Secreted protein HLHFP03

ABSTRACT

The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.

FIELD OF THE INVENTION

[0001] This invention relates to newly identified polynucleotides andthe polypeptides encoded by these polynucleotides, uses of suchpolynucleotides and polypeptides, and their production.

BACKGROUND OF THE INVENTION

[0002] Unlike bacterium, which exist as a single compartment surroundedby a membrane, human cells and other eucaryotes are subdivided bymembranes into many functionally distinct compartments. Eachmembrane-bounded compartment, or organelle, contains different proteinsessential for the function of the organelle. The cell uses “sortingsignals,” which are amino acid motifs located within the protein, totarget proteins to particular cellular organelles.

[0003] One type of sorting signal, called a signal sequence, a signalpeptide, or a leader sequence, directs a class of proteins to anorganelle called the endoplasmic reticulum (ER). The ER separates themembrane-bounded proteins from all other types of proteins. Oncelocalized to the ER, both groups of proteins can be further directed toanother organelle called the Golgi apparatus. Here, the Golgidistributes the proteins to vesicles, including secretory vesicles, thecell membrane, lysosomes, and the other organelles.

[0004] Proteins targeted to the ER by a signal sequence can be releasedinto the extracellular space as a secreted protein. For example,vesicles containing secreted proteins can fuse with the cell membraneand release their contents into the extracellular space—a process calledexocytosis. Exocytosis can occur constitutively or after receipt of atriggering signal. In the latter case, the proteins are stored insecretory vesicles (or secretory granules) until exocytosis istriggered. Similarly, proteins residing on the cell membrane can also besecreted into the extracellular space by proteolytic cleavage of a“linker” holding the protein to the membrane.

[0005] Despite the great progress made in recent years, only a smallnumber of genes encoding human secreted proteins have been identified.These secreted proteins include the commercially valuable human insulin,interferon, Factor VIII, human growth hormone, tissue plasminogenactivator, and erythropoeitin. Thus, in light of the pervasive role ofsecreted proteins in human physiology, a need exists for identifying andcharacterizing novel human secreted proteins and the genes that encodethem. This knowledge will allow one to detect, to treat, and to preventmedical disorders by using secreted proteins or the genes that encodethem.

SUMMARY OF THE INVENTION

[0006] The present invention relates to novel polynucleotides and theencoded polypeptides. Moreover, the present invention relates tovectors, host cells, antibodies, and recombinant methods for producingthe polypeptides and polynucleotides. Also provided are diagnosticmethods for detecting disorders related to the polypeptides, andtherapeutic methods for treating such disorders. The invention furtherrelates to screening methods for identifying binding partners of thepolypeptides.

DETAILED DESCRIPTION

[0007] Definitions

[0008] The following definitions are provided to facilitateunderstanding of certain terms used throughout this specification.

[0009] In the present invention, “isolated” refers to material removedfrom its original environment (e.g., the natural environment if it isnaturally occurring), and thus is altered “by the hand of man” from itsnatural state. For example, an isolated polynucleotide could be part ofa vector or a composition of matter, or could be contained within acell, and still be “isolated” because that vector, composition ofmatter, or particular cell is not the original environment of thepolynucleotide.

[0010] In the present invention, a “secreted” protein refers to thoseproteins capable of being directed to the ER, secretory vesicles, or theextracellular space as a result of a signal sequence, as well as thoseproteins released into the extracellular space without necessarilycontaining a signal sequence. If the secreted protein is released intothe extracellular space, the secreted protein can undergo extracellularprocessing to produce a “mature” protein. Release into the extracellularspace can occur by many mechanisms, including exocytosis and proteolyticcleavage.

[0011] As used herein, a “polynucleotide” refers to a molecule having anucleic acid sequence contained in SEQ ID NO:X or the cDNA containedwithin the clone deposited with the ATCC. For example, thepolynucleotide can contain the nucleotide sequence of the full lengthcDNA sequence, including the 5′ and 3′ untranslated sequences, thecoding region, with or without the signal sequence, the secreted proteincoding region, as well as fragments, epitopes, domains, and variants ofthe nucleic acid sequence. Moreover, as used herein, a “polypeptide”refers to a molecule having the translated amino acid sequence generatedfrom the polynucleotide as broadly defined.

[0012] In the present invention, the full length sequence identified asSEQ ID NO:X was often generated by overlapping sequences contained inmultiple clones (contig analysis). A representative clone containing allor most of the sequence for SEQ ID NO:X was deposited with the AmericanType Culture Collection (“ATCC”). As shown in Table 1, each clone isidentified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number.The ATCC is located at 10801 University Boulevard, Manassas, Va.20110-2209, USA. The ATCC deposit was made pursuant to the terms of theBudapest Treaty on the international recognition of the deposit ofmicroorganisms for purposes of patent procedure.

[0013] A “polynucleotide” of the present invention also includes thosepolynucleotides capable of hybridizing, under stringent hybridizationconditions, to sequences contained in SEQ ID NO:X, the complementthereof, or the cDNA within the clone deposited with the ATCC.“Stringent hybridization conditions” refers to an overnight incubationat 42° C. in a solution comprising 50% formamide. 5×SSC (750 mM NaCl, 75mM sodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt'ssolution, 10% dextran sulfate, and 20 μg/ml denatured, sheared salmonsperm DNA, followed by washing the filters in 0.1×SSC at about 65° C.

[0014] Also contemplated are nucleic acid molecules that hybridize tothe polynucleotides of the present invention at lower stringencyhybridization conditions. Changes in the stringency of hybridization andsignal detection are primarily accomplished through the manipulation offormamide concentration (lower percentages of formamide result inlowered stringency); salt conditions, or temperature. For example, lowerstringency conditions include an overnight incubation at 37° C. in asolution comprising 6×SSPE (20×SSPE =3M NaCl; 0.2M NaH₂PO₄; 0.02M EDTA.pH 7.4), 0.5% SDS, 30% formamide, 100 ug/ml salmon sperm blocking DNA;followed by washes at 50° C. with 1×SSPE, 0.1% SDS. In addition, toachieve even lower stringency, washes performed following stringenthybridization can be done at higher salt concentrations (e.g. 5×SSC).

[0015] Note that variations in the above conditions may be accomplishedthrough the inclusion and/or substitution of alternate blocking reagentsused to suppress background in hybridization experiments. Typicalblocking reagents include Denhardt's reagent, BLOTTO, heparin, denaturedsalmon sperm DNA, and commercially available proprietary formulations.The inclusion of specific blocking reagents may require modification ofthe hybridization conditions described above, due to problems withcompatibility.

[0016] Of course, a polynucleotide which hybridizes only to polyA+sequences (such as any 3′ terminal polyA+ tract of a cDNA shown in thesequence listing), or to a complementary stretch of T (or U) residues,would not be included in the definition of “polynucleotide,” since sucha polynucleotide would hybridize to any nucleic acid molecule containinga poly (A) stretch or the complement thereof (e.g., practically anydouble-stranded cDNA clone).

[0017] The polynucleotide of the present invention can be composed ofany polyribonucleotide or polydeoxribonucleotide, which may beunmodified RNA or DNA or modified RNA or DNA. For example,polynucleotides can be composed of single- and double-stranded DNA, DNAthat is a mixture of single- and double-stranded regions, single- anddouble-stranded RNA, and RNA that is mixture of single- anddouble-stranded regions, hybrid molecules comprising DNA and RNA thatmay be single-stranded or, more typically, double-stranded or a mixtureof single- and double-stranded regions. In addition, the polynucleotidecan be composed of triple-stranded regions comprising RNA or DNA or bothRNA and DNA. A polynucleotide may also contain one or more modifiedbases or DNA or RNA backbones modified for stability or for otherreasons. “Modified” bases include, for example, tritylated bases andunusual bases such as inosine. A variety of modifications can be made toDNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically,or metabolically modified forms.

[0018] The polypeptide of the present invention can be composed of aminoacids joined to each other by peptide bonds or modified peptide bonds,i.e., peptide isosteres, and may contain amino acids other than the 20gene-encoded amino acids. The polypeptides may be modified by eithernatural processes, such as posttranslational processing, or by chemicalmodification techniques which are well known in the art. Suchmodifications are well described in basic texts and in more detailedmonographs, as well as in a voluminous research literature.Modifications can occur anywhere in a polypeptide, including the peptidebackbone, the amino acid side-chains and the amino or carboxyl termini.It will be appreciated that the same type of modification may be presentin the same or varying degrees at several sites in a given polypeptide.Also, a given polypeptide may contain many types of modifications.Polypeptides may be branched, for example, as a result ofubiquitination, and they may be cyclic, with or without branching.Cyclic, branched, and branched cyclic polypeptides may result fromposttranslation natural processes or may be made by synthetic methods.Modifications include acetylation, acylation, ADP-ribosylation,amidation, covalent attachment of flavin, covalent attachment of a hememoiety, covalent attachment of a nucleotide or nucleotide derivative,covalent attachment of a lipid or lipid derivative, covalent attachmentof phosphotidylinositol, cross-linking, cyclization, disulfide bondformation, demethylation, formation of covalent cross-links, formationof cysteine, formation of pyroglutamate, formylation,gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation,iodination, methylation, myristoylation, oxidation, pegylation,proteolytic processing, phosphorylation, prenylation, racemization,selenoylation, sulfation, transfer-RNA mediated addition of amino acidsto proteins such as arginylation, and ubiquitination. (See, forinstance, PROTEINS-STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E.Creighton, W. H. Freeman and Company, New York (1993); POSTTRANSLATIONALCOVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press,New York, pgs. 1-12 (1983); Seifter et al., Meth Enzymol 182:626-646(1990); Rattan et al., Ann NY Acad Sci 663:48-62 (1992).)

[0019] “SEQ ID NO:X” refers to a polynucleotide sequence while “SEQ IDNO:Y” refers to a polypeptide sequence, both sequences identified by aninteger specified in Table 1.

[0020] “A polypeptide having biological activity” refers to polypeptidesexhibiting activity similar, but not necessarily identical to, anactivity of a polypeptide of the present invention, including matureforms, as measured in a particular biological assay, with or withoutdose dependency. In the case where dose dependency does exist, it neednot be identical to that of the polypeptide, but rather substantiallysimilar to the dose-dependence in a given activity as compared to thepolypeptide of the present invention (i.e., the candidate polypeptidewill exhibit greater activity or not more than about 25-fold less and,preferably, not more than about tenfold less activity, and mostpreferably, not more than about three-fold less activity relative to thepolypeptide of the present invention.)

[0021] Polynucleotides and Polypeptides of the Invention

[0022] Features of Protein Encoded by Gene No: 1

[0023] This gene is expressed primarily in cerebellum.

[0024] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, neuraldisorders, particularly damage to the cerebellum or additional CNStissues caused by injuries, which include, but are not limited to,trauma or ischemia. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thecentral nervous system (CNS), expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., neural, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0025] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 150 as residues: Pro-7 to Cys-21, Leu-25 to Ser-30.

[0026] The tissue distribution in cerebellum indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection, treatment, and/or prevention of neurodegenerativedisease states, behavioral disorders, or inflammatory conditions whichinclude, but are not limited to Alzheimer's Disease, Parkinson'sDisease, Huntington's Disease, Tourette Syndrome, meningitis,encephalitis, demyelinating diseases, peripheral neuropathies,neoplasia, trauma, congenital malformations, spinal cord injuries,ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania,dementia, paranoia, obsessive compulsive disorder, depression, panicdisorder, learning disabilities, ALS, psychoses, autism, and alteredbehaviors, including disorders in feeding, sleep patterns, balance, andperception.

[0027] In addition, elevated expression of this gene product in regionsof the brain indicates it plays a role in normal neural function.Potentially, this gene product is involved in synapse formation,neurotransmission, learning, cognition, homeostasis, or neuronaldifferentiation or survival. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tumors andtissues.

[0028] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:11 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1868 of SEQID NO:11, b is an integer of 15 to 1882, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:11, and whereb is greater than or equal to a+14.

[0029] Features of Protein Encoded by Gene No: 2

[0030] The translation product of this gene was found to have homologyto the human env endogenous retrovirus protein (See Genbank AccessionNo, gi|757872), which is thought to play a contributing role in theevents leading up to the onset of cancer or of proliferative disordersin teratocarcinoma cell lines. In specific embodiments, polypeptides ofthe invention comprise the following amino acid sequence:VDPRVRRFWEDPEYPPVAVMSRLMLRRIPTVMSNTHRTQPSTWEQIKKLSQMVGENLRKAGQPVT (SEQID NO: 289), VRRFWEDPEYPPVAVMSRLMLRRIP (SEQ ID NO: 290),SNTHRTQPSTWEQIKKLSQMVGENLRK (SEQ ID NO: 291),SACHSHTVFNWSEQNGQMVQMVRRMARVPIIWNHGSIGAPQPQMIWPIVGAKHKDLWQLLIALNKIKIWERIKKHLEGHSANLSLDIAKYIYIFKASQAHLTLMPELECSKELQTD(SEQ ID NO: 292), MARVPIIWNHGSIGAPQPQMIWPIV (SEQ ID NO: 293),RIKKHLEGHSANLSL DIAKYIYIFKASQAHLT (SEQ ID NO: 294),VFLQQGLTQRSVILIGHICQFWLAIMPGYNHFMTQLHMLSGLNIYHNKSAPIIEAYHPQKSICKQN (SEQID NO: 295), IGHICQFWLAIMPGYNHFMTQLHMLSGL (SEQ ID NO: 296),SIPGTPDLNARTGVLEGAADRLAASNPLKWIKTLRSSVISMMIVLLICVVCLYIVCRC (SEQ ID NO:297), VLEGAADRLAASNPLKWIKTLRSSVIS (SEQ ID NO: 298),LTVTKLPWLFIALQNKRMGTSWEQAPKSGHKLAPKLVINKISAALSHACDSLTPTLEGCRFTGMRARNNWPTQGG (SEQ ID NO: 299), and/or MGTSWEQAPKSGHKLAPKLVINKISAALS (SEQID NO: 300). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0031] This gene is expressed primarily in PHA stimulated T-cells.

[0032] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of thefollowing diseases and conditions which include, but are not limited to,immune disorders, particularly autoimmune, inflammatory, orimmunodeficiency diseases, in addition to, proliferative conditions suchas cancers. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, hematopoietic, teratocarcinoma, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum; plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0033] The tissue distribution in T-cells indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thediagnosis, treatment, and/or prevention of a variety of immune systemdisorders. The expression of this gene product indicates a role in theregulation of the proliferation; survival; differentiation; and/oractivation of potentially all hematopoietic cell lineages, includingblood stem cells. This gene product may be involved in the regulation ofcytokine production, antigen presentation, or other processes that mayalso suggest a usefulness in the treatment of cancer e.g. by boostingimmune responses. Since the gene is expressed in cells of lymphoidorigin, the natural gene product may be involved in immune functions.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,and leukemia.

[0034] In addition, this gene product may have commercial utility in theexpansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. The protein may also show utility in the development ofnovel inhibitors to viral infections, or the protein may be useful inthe development of novel vectors, such as those used in gene therapy,and/or immuno-therapy which could lead to the amelioration of disease ofdisease states. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tumors and tissues.

[0035] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO: 12 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1576 of SEQID NO: 12, b is an integer of 15 to 1590, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:12, and whereb is greater than or equal to a+14.

[0036] Features of Protein Encoded by Gene No: 3

[0037] The translation product of this gene was shown to have homologyto the human retrovirus-related reverse transcriptase pseudogene (SeeGenbank Accession No. pir|A25313|GNHUL1).In specific embodiments,polypeptides of the invention comprise the following amino acidsequence: STHASVQKKDLTKFSAHSWLKKKKTFRKMIMEEIFLNLIKNIYKSPYSQCNT (SEQ IDNO: 301), VRSEKGFDKIQCPFMVK (SEQ ID NO: 302),FSKPSSYKTYIPKINLHFYILLMNIWETIKIVPLNNCFTKMNYLGI (SEQ ID NO: 303),KKETKLSLFANDMI (SEQ ID NO: 304), and/or SPLLFNILLEVLSSAVRKEKELK (SEQ IDNO: 305). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0038] This gene is expressed primarily in PHA activated T cells.

[0039] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions: immune or hematopoietic disorders, particularlyinflammation, immunodeficiencies, and autoimmune diseases. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, hematopoietic, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0040] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 152 as residues: Ile-14 to Thr-24.

[0041] The tissue distribution in T-cells indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thediagnosis, treatment, and/or prevention of a variety of immune systemdisorders. The expression of this gene product indicates a role in theregulation of the proliferation; survival; differentiation; and/oractivation of potentially all hematopoietic cell lineages, includingblood stem cells. This gene product may be involved in the regulation ofcytokine production, antigen presentation, or other processes that mayalso suggest a usefulness in the treatment of cancer e.g. by boostingimmune responses. Since the gene is expressed in cells of lymphoidorigin, the natural gene product may be involved in immune functions.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,and leukemia.

[0042] In addition, this gene product may have commercial utility in theexpansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Alternatively, the homology to a reverse transcriptase humangene may implicate this gene as providing utility in the understandingof host-viral interactions, particularly those involving retrovirusesand other integration-dependent viruses. Moreover, the protein may showutility in the development of novel inhibitors to viral infection, andthus to the amelioration of human diseases and conditions. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0043] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:13 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1359 of SEQID NO:13, b is an integer of 15 to 1373, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:13, and whereb is greater than or equal to a+14.

[0044] Features of Protein Encoded by Gene No: 4

[0045] The translation product of this gene shares sequence homologywith npdcf-1 which is thought to be important in promoting the survivalof bi-potential glial progenitor cells (See Genbank Accession No.gi|456107). One embodiment of this gene comprises polypeptides of thefollowing amino acid sequence:LRRPSTPLRRPWLHLQLPRISLGDQRLAQSAEMYHYQHQRQQMLSLERHKEPPKELDTALRMRRMRTETSRCTSARAWPRPGKWRCATICSTTPHCPRPCRPPAHRLHCHDLEADRRPLAPR(SEQ ID NO: 306),RATQGAGHGSSDEENEDGDFTVYECPGMAPTGEMEVRNHLFDHAALSAPLPAPSSPLALP (SEQ ID NO:307), KAEYATAKALATPAATPDLAWGPAPGTERGDVPLPAPTATDVVPGAA (SEQ ID NO: 308),SAEMYHYQHQRQQML (SEQ ID NO: 309), LERHKEPPKEL (SEQ ID NO: 310),AKCPPGAHACGP (SEQ ID NO: 311), PVHMSPLEP (SEQ ID NO: 312), WCRLQREIRLTQ(SEQ ID NO: 313), SSDEENEDGDFTVYECPG (SEQ ID NO: 314), APTGEMEVRN (SEQID NO: 315), CPGSLDCALK (SEQ ID NO: 316),RATQGAGHGSSDEENEDGDFTVYECPGMAPTGEMEVRNHLFDHAALSAPLPAPSSPLALP (SEQ ID NO:317), NEDGDFTVYECPGMAPTGEMEV (SEQ ID NO: 318),RPTRPSSSCVLPRCLRCSRRGARSPRRAPGLAVPCCPGGGAEGWRRRCLRPPRGTCGCCGCCSPASSSAPPCVEPPPATRNVAACPGSLDCALKKRASVLLVHMPVGLPSALPXGTAKACFAXMRRASXGGRAQPXLEMRLIPGPRELARKGIWTSIPP(SEQ ID NO: 319), RCLRCSRRGARSPRRAPGLAVPCCP (SEQ ID NO: 320), and/orGSLDCALKKRASVLLVHMPVGLPSALPXGTAKAC (SEQ ID NO: 321). Additionalembodiments is the polynucleotides encoding these polypeptides.

[0046] This gene is expressed primarily in cerebellum, synovial sarcoma,and to a lesser extent, in several other cancer cell lines.

[0047] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, neural orskeletal disorders, particularly tumors characterized by cells of arelatively undifferentiated state, including neural tumors. Similarly,polypeptides and antibodies directed to those polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the synovial fluid, prostate, breastand uterus, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,neural, skeletal, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0048] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 153 as residues: Pro-6 to Arg-11, Glu-52 to Gly-59.

[0049] The tissue distribution in the cerebellum, combined with thehomology to the human npdcf-1 protein indicates that polynucleotides andpolypeptides corresponding to this gene are useful for diagnosing andtreating tumors that contain relatively high numbers of undifferentiatedcells. Moreover, this gene is useful for the detection, treatment,and/or prevention of neurodegenerative disease states and behaviouraldisorders such as Alzheimers Disease, Parkinsons Disease, HuntingtonsDisease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia,obsessive compulsive disorder, panic disorder, learning disabilities,ALS, psychoses, autism, and altered behaviors, including disorders infeeding, sleep patterns, balance, and perception.

[0050] In addition, the gene or gene product may also play a role in thetreatment and/or detection of developmental disorders associated withthe developing embryo, sexually-linked disorders, or disorders of thecardiovascular system. Alternatively, the expression of this geneproduct in synovium would suggest a role in the detection and treatmentof disorders and conditions affecting the skeletal system, in particularosteoporosis, bone cancer, as well as, disorders afflicting connectivetissues (e.g., arthritis, trauma, tendonitis, chrondomalacia andinflammation), such as in the diagnosis or treatment of variousautoimmune disorders such as rheumatoid arthritis, lupus, scleroderma,and dermatomyositis as well as dwarfism, spinal deformation, andspecific joint abnormalities as well as chondrodysplasias (i.e.spondyloepiphyseal dysplasia congenita, familial osteoarthritis,Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).

[0051] Moreover, the protein may be useful for inducing astroglialproliferation and promoting neuronal survival, in addition to otherhighly vascular tissues. The protein can also be used to regulatecellular metabolism (e.g., through the modulation of proteinexpression). Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0052] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:14 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1128 of SEQID NO: 14, b is an integer of 15 to 1142, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO: 14, andwhere b is greater than or equal to a+14.

[0053] Features of Protein Encoded by Gene No: 5

[0054] The translation product of this gene was found to have homologyto the RoBo-1 protein from Rattus norvegicus (See Genbank AccessionNo.gi|2895563 (AF041083)) which is thought to be important as a mediatorin bone remodeling. In specific embodiments, polypeptides of theinvention comprise the following amino acid sequence:DSHQARSRRLEALWSPSLGEVSSST (SEQ ID NO: ). Polynucleotides encoding thesepolypeptides are also encompassed by the invention.

[0055] This gene is expressed primarily in colon, pituitary, and to alesser extent in fetal lung and fibrosarcoma.

[0056] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,endocrine, gastrointestinal, pulmonary, skeletal, or developmental andproliferative disorders, particularly those effecting theGut/pituitary/hypothalamic axis. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe digestive system and regulation of feeding, expression of this geneat significantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., gastrointesinal, endocrine,developmental, skeletal, pulmonary, and cancerous and wounded tissues)or bodily fluids (e.g., lymph, serum, plasma, amniotic fluid, pulmonarysurfactant or sputum, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0057] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 154 as residues: Asn-26 to Cys-32, Cys-100 to Leu-112,Cys-128 to Ser-135.

[0058] The tissue distribution in colon and pituitary indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treating disorders related to the intake and utilization of foodsince this gene is expressed in the digestive tract and a CNS siteinvolved in regulation of weight homeostasis. The secreted protein canalso be used to determine biological activity, to raise antibodies, astissue markers, to isolate cognate ligands or receptors, to identifyagents that modulate their interactions, and as nutritional supplements.It may also have a very wide range of biological activities. Typical ofthese are cytokine, cell proliferation/differentiation modulatingactivity or induction of other cytokines;immunostimulating/immunosuppressant activities (e.g., for treating humanimmunodeficiency virus infection, cancer, autoimmune diseases andallergy); regulation of hematopoiesis (e.g., for treating anemia or asadjunct to chemotherapy); stimulation or growth of bone, cartilage,tendons, ligaments and/or nerves (e.g., for treating wounds, stimulationof follicle stimulating hormone (for control of fertility); chemotacticand chemokinetic activities (e.g., for treating infections, tumors);hemostatic or thrombolytic activity (e.g., for treating hemophilia,cardiac infarction etc.); anti-inflammatory activity (e.g., for treatingseptic shock, Crohn's disease); as antimicrobials; for treatingpsoriasis or other hyperproliferative diseases; for regulation ofmetabolism, and behavior. Also contemplated is the use of thecorresponding nucleic acid in gene therapy procedures. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0059] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO: 15 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1020 of SEQID NO:15, b is an integer of 15 to 1034, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:15, and whereb is greater than or equal to a+14.

[0060] Features of Protein Encoded by Gene No: 6

[0061] The translation product of this gene shares sequence homologywith Cortical granule lectin which is thought to be important inblocking polyspermy (See Genbank Accession No. gnl|PID|e1181610). Inspecific embodiments, polypeptides of the invention comprise thefollowing amino acid sequence: RSCKEIKD (SEQ ID NO: 323), GGGWTLVASVHEN(SEQ ID NO: 324), ADYPEGDGNWANYNTFGSA (SEQ ID NO: 325), ATSDDYKNPGYYDI(SEQ ID NO: 326), CIGGGGYFPEA (SEQ ID NO: 327), DSDKIT (SEQ ID NO: 329),YQTFCDMT (SEQ ID NO: 330), and/or EITEAAVLLFY (SEQ ID NO: 328).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0062] This gene is expressed primarily in benign and metastatic colon,and to a lesser extent in HEL cells.

[0063] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,gastrointestinal, reproductive, or developmental disorders, particularlycancer, or inflammatory conditions. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the digestive system, expression of this gene atsignificantly higher or lower levels may be detected in certain tissuesor cell types (e.g., gastrointestinal, reproductive, proliferating, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, seminal fluid, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0064] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 155 as residues: Arg-15 to Ser-33, Pro-35 to Cys-41.

[0065] The tissue distribution in colon, combined with the homology tocortical granule lectins indicates that polynucleotides and polypeptidescorresponding to this gene are useful for treating disorders of thecolon. These may include diseases related to damage or chronicinflammation as well as tumors of the colon. The product may also beuseful for the identification of colon cancer metastasis and, as asecreted protein, may have diagnostic and prognostic applications.Moreover, the protein is useful in the treatment, detection, and/orprevention of reproductive disorders, particularly normal testicularfunction, in addition having utility in the development ofcontraceptives, or in the treatment of polyspermy. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tumors andtissues.

[0066] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:16 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1184 of SEQID NO:16, b is an integer of 15 to 1198, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:16, and whereb is greater than or equal to a+14.

[0067] Features of Protein Encoded by Gene No: 7

[0068] This gene is expressed primarily in eight week human embryos.

[0069] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, fetaland/or developmental abnormalities. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the developing fetus, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., developing, differentiating, andcancerous and wounded tissues) or bodily fluids (e.g., amniotic fluid,serum, plasma, lymph, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0070] The tissue distribution in eight week old tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor detecting embryonic abnormalities, in particular congenitalabnormalities, which include, but are not limited to Tay-Sachs disease,phenylkenonuria, galactosemia, hyperlipidemias, porphyrias, and Hurler'ssyndrome. Expression within embryonic tissue and other cellular sourcesmarked by proliferating cells indicates that this protein may play arole in the regulation of cellular division, and may show utility in thediagnosis, treatment, and/or prevention of cancer and otherproliferative disorders. Similarly, developmental tissues rely ondecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0071] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:17 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1433 of SEQID NO:17, b is an integer of 15 to 1447, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:17, and whereb is greater than or equal to a+14.

[0072] Features of Protein Encoded by Gene No: 8

[0073] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:MGKRAHEVRRPPHSRPLHGTPAGWVLDPSGYKDVTQDAEVMEVLQNLYRTKSFLFVGCGETLRDQIFQALFLYSVPNKVDLEHYMLVLKENEDHFFKHQADMLLHGIKVVSYGDCFDHFPGYVQDLATQICKQQSPGHLYSNSWSATPDGRGGP(SEQ ID NO: 331), VLDPSGYKDVTQDAEVMEVLQNLYRT (SEQ ID NO: 332),YSVPNKVDLEHY MLVLKENEDHFFKH (SEQ ID NO: 333), DLATQICKQQSPGHLYSNSWSATPD(SEQ ID NO: 334),RRMKTISLSIRQICFCTESKLYPTGTVLTTFQDMCKTLPLRSANSKAQDICTRIHGVPLLMGEEAHDSDSHASDRGHHTMLPLPAGSFSESSHQAWEVEMLIAWTAPHYWVMHARTVQRGS(SEQ ID NO: 335), TESKLYPTGTVLTTFQDMCKTLPLRSA (SEQ ID NO: 336), and/orLMGEEAH DSDSHASDRGHHTMLPLPAG (SEQ ID NO: 337). Polynucleotides encodingthese polypeptides are also encompassed by the invention.

[0074] This gene is expressed primarily in endothelial cells, and to alesser extent in lymph node, tonsils, heart and spinal cord.

[0075] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, vasculardiseases, such as restenosis, including disorders of the integumentarysystem. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thevascular system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., vascular, integumentary, immune, hematopoietic, neural,cardiovascular, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0076] The tissue distribution in endothelial cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treating diseases of the vasculature including problems associatedwith diabetes and restenosis following angioplasty. Moreover, theprotein is useful in the detection, treatment, and/or prevention of avariety of other vascular conditions, which include, but are not limitedto, stroke, microvascular disease, aneurysm, vascular leak syndrome, orembolism. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0077] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:18 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1408 of SEQID NO:18, b is an integer of 15 to 1422, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:18, and whereb is greater than or equal to a+14.

[0078] Features of Protein Encoded by Gene No: 9

[0079] The translation product of this gene was shown to have homologyto the Gcap1 gene product of Mus musculus, which is specificallyexpressed in cerebellum and appears to be developmentally regulated (SeeGenbank Accession No. gi|862343). In specific embodiments, polypeptidesof the invention comprise the following amino acid sequence:LCAVEKTRTFTRGDCGPNRHHKHVLKAKDNNHIQRHQFSSTLEFSSNSTDGLKYICVYLYVCTHPCIYIYLSAHTLHMYTHYLCKI(SEQ ID NO:338), SSTLEFSSNSTDGLKYICVYLYVCTHPCIY (SEQ ID NO:339),STSVCICTCAHTHVYIFIYLHTHYICIHTIYVKYNICIMHINSNKCICVIFKIEQLYLEVVNAENWFYC(SEQ ID NO:340), IHTIYVKYNICIMHIN SNKCICVIFKIEQLY (SEQ ID NO:341),and/or NSAVTVQMA (SEQ ID NO:342). Polynucleotides encoding thesepolypeptides are also encompassed by the invention.

[0080] This gene is expressed primarily in fetal lung, endothelial cellsand to a lesser extent, in astrocytes and fetal brain.

[0081] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,vasdcular, developmental, neural, or proliferative conditions,particularly endothelial cell proliferation, such as occurs inrestenosis. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thevascular system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., developmental, neural, vascular, and cancerous and woundedtissues) or bodily fluids (e.g., amniotic fluid, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression,level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0082] The tissue distribution in fetal brain, in addition to thehomology to a brain-specific regulatory protein indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection, treatment, or prevention of neurodegenerative diseasestates and behavioural disorders such as Alzheimers Disease, ParkinsonsDisease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania,dementia, paranoia, obsessive compulsive disorder, panic disorder,learning disabilities, ALS, psychoses, autism, and altered behaviors,including disorders in feeding, sleep patterns, balance, and perception.In addition, the gene or gene product may also play a role in thetreatment and/or detection of developmental disorders associated withthe developing embryo, sexually-linked disorders, or disorders of thecardiovascular system.

[0083] Alternatively,the tissue distribution indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treating abnormal proliferation of endothelial cells such as occursupon injury to the lung or arteries. Moreover, this protein may play arole in the regulation of cellular division, and may show utility in thediagnosis and treatment of cancer and other proliferative disorders.Similarly, developmental tissues rely on decisions involving celldifferentiation and/or apoptosis in pattern formation. Thus this proteinmay also be involved in apoptosis or tissue differentiation and couldagain be useful in cancer therapy. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0084] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:19 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1093 of SEQID NO:19, b is an integer of 15 to 1107, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:19, and whereb is greater than or equal to a+14.

[0085] Features of Protein Encoded by Gene No: 10

[0086] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: TKTSTPLR (SEQ ID NO: 343).Polynucleotides encoding these polypeptides are also encompassed by theinvention. The gene encoding the disclosed cDNA is believed to reside onchromosome 12. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 12.

[0087] This gene is expressed primarily in infant brain and fetaltissues.

[0088] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,developmental abnormalities or neural disorders, particularlygestational conditions, such as spina bifida. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the central nervous system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., developing, neural,differentiating, and cancerous and wounded tissues) or bodily fluids(e.g., amniotic fluid, serum, lymph, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0089] The tissue distribution in infant brain and fetal tissuessuggests that the protein product of this clone is useful for thedetection/treatment of neurodegenerative disease states and behaviouraldisorders such as Alzheimers Disease, Parkinsons Disease, HuntingtonsDisease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia,obsessive compulsive disorder, panic disorder, learning disabilities,ALS, psychoses, autism, and altered behaviors, including disorders infeeding, sleep patterns, balance, and perception. In addition, the geneor gene product may also play a role in the treatment and/or detectionof developmental disorders associated with the developing embryo,sexually-linked disorders, or disorders of the cardiovascular system.Alternatively, the tissue distribution suggests that the protein productof this clone is useful for the diagnosis, treatment, and/or preventionof cancer and other proliferative disorders. Moreover, the expressionwithin fetal tissue and other cellular sources marked by proliferatingcells suggests that this protein may play a role in the regulation ofcellular division. Similarly, embryonic development also involvesdecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0090] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:20 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1169 of SEQID NO:20, b is an integer of 15 to 1183, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:20, and whereb is greater than or equal to a+14.

[0091] Features of Protein Encoded by Gene No: 11

[0092] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: VCIPGAAGLSVLLG (SEQ ID NO: 344).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0093] This gene is expressed primarily in fetal kidney.

[0094] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,urogenital, renal, or developmental disorders, particularly renalfailure, tumors of the kidney, and/or developmental abnormalitiesassociated with the kidney. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe renal system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., urological, renal, developmental, and cancerous and woundedtissues) or bodily fluids (e.g., amniotic fluid, lymph, serum, plasma,urine, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0095] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 160 as residues: Gln-26 to Gln-34.

[0096] The tissue distribution in fetal kidney indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of cancer and otherproliferative disorders, particularly renal disorders. Expression withinembryonic tissue and other cellular sources marked by proliferatingcells indicates that this protein may play a role in the regulation ofcellular division. Similarly, embryonic development also involvesdecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy.

[0097] Moreover, the protein product of this gene could be used in thetreatment and/or detection of kidney diseases including nephritus, renaltubular acidosis, proteinuria, pyuria, edema, pyelonephritis,hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis,hematuria, renal colic and kidney stones, in addition to Wilm's TumorDisease, and congenital kidney abnormalities such as horseshoe kidney,polycystic kidney, and Falconi's syndrome. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0098] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:21 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1406 of SEQID NO:21, b is an integer of 15 to 1420, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:21, and whereb is greater than or equal to a+14.

[0099] Features of Protein Encoded by Gene No: 12

[0100] The gene encoding the disclosed cDNA is believed to reside onchromosome 17. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 17.

[0101] This gene is expressed primarily in breast, fetal kidney, andT-cells.

[0102] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive, immune, developmental, or renal disorders, particularlyautoimmune diseases, chronic inflammatory conditions, or urogenitaldisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, reproductive, cancerous and wounded tissues) or bodily fluids(e.g., breast milk, lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0103] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 161 as residues: His-2 to Lys-7, Ser-28 to Glu-35.

[0104] The tissue distribution in breast and T-cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Moreover, the expression of this gene productindicates a role in regulating the proliferation; survival;differentiation; and/or activation of potentially all hematopoietic celllineages, including blood stem cells. This gene product may be involvedin the regulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancere.g. by boosting immune responses.

[0105] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, andleukemia. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tumors and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types.

[0106] Alternatively, the expression within fetal tissue indicates thisprotein may play a role in the regulation of cellular division, and mayshow utility in the diagnosis and treatment of cancer and otherproliferative disorders. Similarly, developmental tissues rely ondecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0107] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:22 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1561 of SEQID NO:22, b is an integer of 15 to 1575, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:22, and whereb is greater than or equal to a+14.

[0108] Features of Protein Encoded by Gene No: 13

[0109] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:SILPVEMAAAVAGMLRGGLLPQAGRLPTLQTVRYGSKAVTRHRRV (SEQ ID NO: 345), and/orAGMLRGGLLPQAGRLPTLQTVRYGSK (SEQ ID NO: 346). Polynucleotides encodingthese polypeptides are also encompassed by the invention.

[0110] This gene is expressed primarily in the frontal cortex of thebrain.

[0111] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, neuraldisorders, particularly neurodegenerative disorders, ischemia,Alzheimer's, or Parkinson's. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe central nervous system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., neural, and cancerous and wounded tissues) or bodilyfluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0112] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 162 as residues: Glu-31 to Gly-37.

[0113] The tissue distribution in frontal cortex indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection/treatment of neurodegenerative disease states andbehavioural disorders such as Alzheimers Disease, Parkinsons Disease,Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia,paranoia, obsessive compulsive disorder, panic disorder, learningdisabilities, ALS, psychoses, autism, and altered behaviors, includingdisorders in feeding, sleep patterns, balance, and perception. Inaddition, the gene or gene product may also play a role in the treatmentand/or detection of developmental disorders associated with thedeveloping embryo. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tumors and tissues.

[0114] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:23 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 527 of SEQID NO:23, b is an integer of 15 to 541, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:23, and where bis greater than or equal to a+14.

[0115] Features of Protein Encoded by Gene No: 14

[0116] The gene encoding the disclosed cDNA is believed to reside onchromosome 1. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 1.

[0117] This gene is expressed primarily in ovary, and to a lesserextent, in infant brain.

[0118] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive, neural, or developmental disorders, particularly cancersand other diseases of the reproductive system including ovarian cystsand hormonal disorders. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thefemale reproductive system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., reproductive, neural, developmental, and cancerous andwounded tissues) or bodily fluids (e.g., amniotic fluid, lymph, seminalfluid, serum, plasma, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0119] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 163 as residues: Ser-32 to Glu-37.

[0120] The tissue distribution in ovarian tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and intervention of ovarian tumors, in addition to othertumors where expression has been indicated. Alternatively, expressionwithin the fetal brain indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the detection/treatment ofneurodegenerative disease states and behavioural disorders such asAlzheimers Disease, Parkinsons Disease, Huntingtons Disease, TouretteSyndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsivedisorder, panic disorder, learning disabilities, ALS, psychoses ,autism, and altered behaviors, including disorders in feeding, sleeppatterns, balance, and perception. In addition, the gene or gene productmay also play a role in the treatment and/or detection of developmentaldisorders associated with the developing embryo.

[0121] Moreover, the expression within fetal tissue indicates thisprotein may play a role in the regulation of cellular division, and mayshow utility in the diagnosis and treatment of cancer and otherproliferative disorders. Similarly, developmental tissues rely ondecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0122] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:24 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 819 of SEQID NO:24, b is an integer of 15 to 833, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:24, and where bis greater than or equal to a+14.

[0123] Features of Protein Encoded by Gene No: 15

[0124] The translation product of this gene was shown to have homologyto the highly conserved ras gene which is known to be important in theregulation of cell growth, and thus has been shown to serve as aninducible oncogene in eukaryotic tissues (See Genbank Accession No.gb|Z11804|DDRASX). When tested against PC12 (rat pheochromocytoma cells)and NIH3T3 cell lines, supernatants removed from cells containing thisgene activated the EGR1 (early growth response gene 1) promoter element.Thus, it is likely that this gene activates sensory neuron cells andfibroblasts, in addition to other tissues or cell types, through theEGR1 signal transduction pathway. The EGR1 (early growth responsegene 1) is a separate signal transduction pathway from Jaks-STAT, genescontaining the EGR1 promoter are induced in various tissues and celltypes upon activation, leading the cells to undergo differentiation andproliferation.

[0125] Moreover, contact of cells with supernatant expressing theproduct of this gene has been shown to increase the permeability of theplasma membrane of monocytes to calcium. Thus it is likely that theproduct of this gene is involved in a signal transduction pathway thatis initiated when the product binds a receptor on the surface of theplasma membrane of monocytes, in addition to other cell-lines or tissuecell types, such as immune or hematopoietic cells. Thus, polynucleotidesand polypeptides have uses which include, but are not limited to,activating monocytes.

[0126] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: ARAGQMQNLESARAGRSVSTQTGS (SEQ ID NO:347). Polynucleotides encoding these polypeptides are also encompassedby the invention. The gene encoding the disclosed cDNA is believed toreside on chromosome 13. Accordingly, polynucleotides related to thisinvention are useful as a marker in linkage analysis for chromosome 13.

[0127] This gene is expressed primarily in T-cells.

[0128] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesinvolving immune regulation, which include, but are not limited toautoimmune diseases such as rheumatoid arthritis, lupus, and leukemia.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the immune,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g.,hematopoietic, immune, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0129] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 164 as residues: Ala-28 to His-41, Pro-43 to Gln-64.

[0130] The tissue distribution in T-cells, combined with the detectedEGR1 and calcium flux activities, indicates polynucleotides andpolypeptides corresponding to this gene are useful for the diagnosis,treatment, and/or prevention of a variety of immune system disorders,particularly those dependent upon signalling aberrations. Expression ofthis gene product in T-cells indicates a role in regulating theproliferation; survival; differentiation; and/or activation ofpotentially all hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer—particularly consideringthe homology to a conserved ras gene, and the detected EGR1 biologicalactivity.

[0131] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, andleukemia. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tumors and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0132] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:25 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1541 of SEQID NO:25, b is an integer of 15 to 1555, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:25, and whereb is greater than or equal to a+14.

[0133] Features of Protein Encoded by Gene No: 16

[0134] This gene is expressed primarily in kidney cortex.

[0135] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the kidney including cancer and renal dysfunction, in addition to,endocrine disorders, particularly of the adrenal glands. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the renal system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., urogenital, renal, endocrine,and cancerous and wounded tissues) or bodily fluids (e.g., urine, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0136] The tissue distribution in kidney cortex indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment, diagnosis, and/or prevention of diseases of thekidney including renal failure, nephritus, renal tubular acidosis,proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephroticsyndrome, crush syndrome, glomerulonephritis, hematuria, renal colic andkidney stones, in addition to Wilm's Tumor Disease, and congenitalkidney abnormalities such as horseshoe kidney, polycystic kidney, andFalconi's syndrome. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0137] Many polynucleotide sequences, such as EST sequences are publiclyavailable and accessible through sequence databases. Some of thesesequences are related to SEQ ID NO:26 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1529 of SEQID NO:26, b is an integer of 15 to 1543, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:26, and whereb is greater than or equal to a+14.

[0138] Features of Protein Encoded by Gene No: 17

[0139] This gene is expressed primarily in T-cell lymphoma, and to alesser extent, in bone marrow stromal cells.

[0140] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune orhematopoietic disorders, particularly cancers, such as lymphomas andleukemias. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0141] The tissue distribution in bone marrow stromal cells and T-celllymphoma indicates that polynucleotides and polypeptides correspondingto this gene are useful for the diagnosis, treatment, and/or preventionof a variety of immune or hematopoietic disorders. Expression of thisgene product in T-cells indicates a role in regulating theproliferation; survival; differentiation; and/or activation ofpotentially all hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g., by boostingimmune responses). Since the gene is expressed in cells of lymphoidorigin, the natural gene product may be involved in immune functions.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,and leukemia. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tumors and tissues. In addition, this gene productmay have commercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types.

[0142] Expression in bone marrow cells suggest that polynucleotides andpolypeptides corresponding to this gene are useful for the treatment anddiagnosis of hematopoetic related disorders such as anemia,pancytopenia, leukopenia, thrombocytopenia or leukemia since stromalcells are important in the production of cells of hematopoieticlineages. The uses include bone marrow cell ex vivo culture, bone marrowtransplantation, bone marrow reconstitution, radiotherapy orchemotherapy of neoplasia. The gene product may also be involved inlymphopoiesis, therefore, it can be used in immune disorders such asinfection, inflammation, allergy, immunodeficiency etc. In addition,this gene product may have commercial utility in the expansion of stemcells and committed progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tumorsand tissues.

[0143] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:27 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1248 of SEQID NO:27, b is an integer of 15 to 1262, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:27, and whereb is greater than or equal to a+14.

[0144] Features of Protein Encoded by Gene No: 18

[0145] This gene is expressed primarily in medulloblastoma.

[0146] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, disordersof the central nervous system, including cancers. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the central nervous system, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., neural, cancerous andwounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0147] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 167 as residues: Phe-22 to Leu-28.

[0148] The tissue distribution indicates that polynucleotides andpolypeptides corresponding to this gene are useful for the detection,treatment, and/or prevention of neurodegenerative disease states andbehavioural disorders such as Alzheimers Disease, Parkinsons Disease,Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia,paranoia, obsessive compulsive disorder, panic disorder, learningdisabilities, ALS, psychoses , autism, and altered behaviors, includingdisorders in feeding, sleep patterns, balance, and perception. Inaddition, the gene or gene product may also play a role in the treatmentand/or detection of developmental disorders associated with thedeveloping embryo. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0149] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:28 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 739 of SEQID NO:28, b is an integer of 15 to 753, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:28, and where bis greater than or equal to a+14.

[0150] Features of Protein Encoded by Gene No: 19

[0151] The translation product of this gene was shown to have homologyto the mammalian notch I protein which has been shown to be important inthe regulation of cell-fate during pattern formation and development(See Genbank Accession No. gi|57635). One embodiment of this genecomprises polypeptides of the following amino acid sequence:KHEXHQVSDGALRCFASLADRFTRRGVDPAPLAKHGLTEELLSRMAAAGGTVSGPSSACKPXRSTTGAPSTTADSKLSNQVSTIVSLLSTLCRGSPVVTHDLLRSELPDSIESALQGDERCVLDTMRLVDFLLVLLFEGRKALPKSSAGSTGRIPGLRRLDSSGERSHRQLIDCIRSKDTDALIDAIDTGAFEVNFMDDVGQTLLNWASAFGTQEMVEFLCERGADVNRGQRSSSLHYAACFGRPQVAKTLLRHGANPDLRDEDGKTPLDKARERGHSEVVAILQSPGDWMCPVNKGDDK(SEQ ID NO: 348), PLDKARERGHSEVVAIL (SEQ ID NO: 349), AKTLLRHGANPDLRD(SEQ ID NO: 350), GRGRAWLCRRPVGSWIGAVWNDKPDKETFKKPWQMWTQIHCWNGYRWDXXDXKD(SEQ ID NO: 351), SWIGAVWNDKPDKETFKKPWQMW (SEQ ID NO: 352),KTMADVDPDTLLEWLQMGXGRXKGHATN TP (SEQ ID NO: 353),RGVDPAPLAKHGLTEELLSRMAAAGGTVSGPSSA (SEQ ID NO: 354),RSTTGAPSTTADSKLSNQVSTIVSLLSTLCR (SEQ ID NO: 355),FEVNFMDDVGQTLLNWASAFGTQEMVEFLCERGA (SEQ ID NO: 356), and/orEDGKTPLDKARERGHSEVVAILQSPGDW (SEQ ID NO: 357). An additional embodimentis the polynucleotides encoding these polypeptides.

[0152] This gene is expressed primarily in endothelial cells.

[0153] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, vasculardisorders, particularly diseases involving angiogenic abnormalitiesincluding diabetic retinopathy, macular degeneration, and other diseasesincluding arterioscerosis, stroke, aneurysm, embolism, and cancer.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the vascularsystem, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,endothelial, vascular, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue from an individual not having thedisorder.

[0154] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 168 as residues: Asp-17 to Phe-23.

[0155] The tissue distribution in endothelial cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor treating diseases where an increase or decrease in angiogenesis isindicated and as a factor in the wound healing process. The protein isuseful in the treatment of cancer cells and tissues, particularly ininhibiting angiogenesis of the invading tumor. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0156] Alternatively, considering the homology to the Notch I protein,this gene may show utility in the detection/treatment ofneurodegenerative disease states and behavioural disorders such asAlzheimers Disease, Parkinsons Disease, Huntingtons Disease, TouretteSyndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsivedisorder, panic disorder, learning disabilities, ALS, psychoses ,autism, and altered behaviors, including disorders in feeding, sleeppatterns, balance, and perception. In addition, the gene or gene productmay also play a role in the treatment and/or detection of developmentaldisorders associated with the developing embryo, sexually-linkeddisorders, or disorders of the cardiovascular system. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0157] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:29 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1607 of SEQID NO:29, b is an integer of 15 to 1621, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:29, and whereb is greater than or equal to a+14.

[0158] Features of Protein Encoded by Gene No: 20

[0159] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: TRPTMPNFLWFPKCA (SEQ ID NO: 358).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0160] This gene is expressed primarily in meningioma tissues.

[0161] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, neural orcentral nervous system disorders, particularly cancers of the centralnervous system and endothelium. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe central nervous system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., neural, endothelial, CNS, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0162] The tissue distribution in meningioma tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection/treatment of neurodegenerative disease states andbehavioural disorders such as Alzheimers Disease, Parkinsons Disease,Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia,paranoia, obsessive compulsive disorder, panic disorder, learningdisabilities, ALS, psychoses, autism, and altered behaviors, includingdisorders in feeding, sleep patterns, balance, and perception. Inaddition, the gene or gene product may also play a role in the treatmentand/or detection of developmental disorders associated with thedeveloping embryo, sexually-linked disorders, or disorders of thecardiovascular system.

[0163] Moreover, the protein is useful in inhibiting or amelioratinginfections of the meninges, particular viral infections. In addition,the protein may show utility in the treatment, detection, and/orprevention of such infections and disorders, in addition to degenerativeconditions or congenital defects of the meninges. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0164] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:30 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 907 of SEQID NO:30, b is an integer of 15 to 921, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:30, and where bis greater than or equal to a+14.

[0165] Features of Protein Encoded by Gene No: 21

[0166] The translation product of this gene was shown to have homologyto the retinoic acid receptor gamma-2 which is thought to be importantin the development of, and may be a key determinant for, human breastcancer during aberrant activation (See Genbank Accession No. AA176435).In specific embodiments, polypeptides of the invention comprise thefollowing amino acid sequence.LPPCLAQIFPFFSSGTNLTFCFFVFVFVFVFAELDYRNSYEIEY (SEQ ID NO: 359).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0167] This gene is expressed primarily in ovary, and to a lesserextent, in meningioma.

[0168] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive or neural disorders, particularly ovarian cancer, as wellas, other cancers of the reproductive system, meninges, and endothelialtissue in general. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thefemale reproductive system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., ovarian, reproductive, neural, endothelial, endocrine,and cancerous and wounded tissues) or bodily fluids (e.g., amnioticfluid, lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0169] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 170 as residues: Leu-8 to Gln-18, Thr-26 to Lys-33, Met-39 toCys-46, Ala-62 to Pro-69, Pro-83 to Glu-90.

[0170] The tissue distribution in ovarian tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and intervention of tumors within these tissues, inaddition to other tumors where expression has been indicated. Theprotein may also show utility in the treatment, detection, prevention,and/or amelioration of degenerative conditions or congenital disordersof the meninges, and the brain and spinal cord, in general. Protein, aswell as, antibodies directed against the protein may show utility as atissue-specific marker and/or immunotherapy target for the above listedtumors and tissues.

[0171] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:31 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 2081 of SEQID NO:31, b is an integer of 15 to 2095, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:31, and whereb is greater than or equal to a+14.

[0172] Features of Protein Encoded by Gene No: 22

[0173] This gene is expressed primarily in the spongy tissue fromAlzheimer's brain.

[0174] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, neuraldisorders, which include, but are not limited to Alzheimer's disease andother neurodegenerative diseases. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe central nervous system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., neural, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0175] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 171 as residues: Ser-31 to Ala-37, Ala-50 to Tyr-55, Phe-63to Arg-68, His-83 to Pro-89.

[0176] The tissue distribution in spongy tissue from Alzheimer's patientindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the detection/treatment of neurodegenerative diseasestates and behavioural disorders such as Alzheimers Disease, ParkinsonsDisease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania,dementia, paranoia, obsessive compulsive disorder, panic disorder,learning disabilities, ALS, psychoses , autism, and altered behaviors,including disorders in feeding, sleep patterns, balance, and perception.In addition, the gene or gene product may also play a role in thetreatment and/or detection of developmental disorders associated withthe developing embryo. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0177] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:32 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1824 of SEQID NO:32, b is an integer of 15 to 1838, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:32, and whereb is greater than or equal to a+14.

[0178] Features of Protein Encoded by Gene No: 23

[0179] This gene is expressed primarily in bone marrow cells.

[0180] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune orhematological disorders. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thehematological and immune systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, haematopoeitic, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0181] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 172 as residues: Glu-22 to Ser-33, Leu-47 to Ser-55, Thr-87to Arg-104.

[0182] The tissue distribution in bone marrow cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of hematopoetic related disorders, whichinclude, but are not limited to anemia, pancytopenia, leukopenia,thrombocytopenia or leukemia since stromal cells are important in theproduction of cells of hematopoietic lineages. The uses include bonemarrow cell ex vivo culture, bone marrow transplantation, bone marrowreconstitution, radiotherapy or chemotherapy of neoplasia. The geneproduct may also be involved in lymphopoiesis, therefore, it can be usedin immune disorders such as infection, inflammation, allergy,immunodeficiency etc. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0183] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:33 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 768 of SEQID NO:33, b is an integer of 15 to 782, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:33, and where bis greater than or equal to a+14.

[0184] Features of Protein Encoded by Gene No: 24

[0185] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: LKCTIYGGA (SEQ ID NO: 360).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0186] This gene is expressed primarily in neutrophils.

[0187] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the immune system, including inflammatory diseases and allergies.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the immunesystem, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,immune, haematopoeitic, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0188] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 173 as residues: Gln-36 to Lys-41.

[0189] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product indicates a role inregulating the proliferation; survival; differentiation; and/oractivation of hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses). Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions.

[0190] Therefore it may be also used as an agent for immunologicaldisorders including arthritis, asthma, immunodeficiency diseases such asAIDS, leukemia, rheumatoid arthritis, granulomatous disease,inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia,psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity;immune reactions to transplanted organs and tissues, such ashost-versus-graft and graft-versus-host diseases, or autoimmunitydisorders, such as autoimmune infertility, lense tissue injury,demyelination, systemic lupus erythematosis, drug induced hemolytic,anemia, rheumatoid arthritis, Sjogren's disease, scleroderma andtissues. In addition, this gene product may have commercial utility inthe expansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0191] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:34 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1546 of SEQID NO:34, b is an integer of 15 to 1560, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:34, and whereb is greater than or equal to a+14.

[0192] Features of Protein Encoded by Gene No: 25

[0193] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:HVLWSLLSACWTQFLVYFCCLMILQRTFPPRALRTSPWLSNPMGVKGKKKKGTFME (SEQ ID NO:361), and/or FLVYFCCLMILQRTFPPRALRTSPWLSNPM(SEQ ID NO: 362).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0194] This gene is expressed primarily in neutrophils.

[0195] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune orhematopoietic disorders, including inflammatory diseases and allergies.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the immunesystem, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,immune, haematopoeitic, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0196] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product indicates a role inregulating the proliferation; survival; differentiation; and/oractivation of hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses).

[0197] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immunodeficiency diseases such as AIDS, leukemia,rheumatoid arthritis, granulomatous disease, inflammatory bowel disease,sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,such as T-cell mediated cytotoxicity; immune reactions to transplantedorgans and tissues, such as host-versus-graft and graft-versus-hostdiseases, or autoimmunity disorders, such as autoimmune infertility,lense tissue injury, demyelination, systemic lupus erythematosis, druginduced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,scleroderma and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0198] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:35 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1078 of SEQID NO:35, b is an integer of 15 to 1092, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:35, and whereb is greater than or equal to a+14.

[0199] Features of Protein Encoded by Gene No: 26

[0200] This gene is expressed primarily in neutrophils.

[0201] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune orhematopoietic disorders, including inflammatory conditions andallergies. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, hematopoietic, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0202] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 175 as residues: Lys-9 to Leu-16, Ser-33 to Met-43.

[0203] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product indicates a role inregulating the proliferation; survival; differentiation; and/oractivation of hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses).

[0204] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immunodeficiency diseases such as AIDS, leukemia,rheumatoid arthritis, granulomatous disease, inflammatory bowel disease,sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,such as T-cell mediated cytotoxicity; immune reactions to transplantedorgans and tissues, such as host-versus-graft and graft-versus-hostdiseases, or autoimmunity disorders, such as autoimmune infertility,lense tissue injury, demyelination, systemic lupus erythematosis, druginduced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,scieroderma and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0205] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:36 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1139 of SEQID NO:36, b is an integer of 15 to 1153, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:36, and whereb is greater than or equal to a+14.

[0206] Features of Protein Encoded by Gene No: 27

[0207] The translation product of this gene was shown to have homologyto the intrinsic factor-B 12 receptor precursor of Rattus norvegicuswhich is thought to be important in development (See Genbank AccessionNo. gi|2961490 (AF022247)). One embodiment of this gene comprisespolypeptides of the following amino acid sequence:DCNRDYHKAFGNLRSPGWPDNYDNDXDCXVTLTAPQNHHSGIVENAETISWR (SEQ ID NO: 363),FGNLRSPGWPDNYDN (SEQ ID NO: 364), ASFYRTS (SEQ ID NO: 366), and/orAPQNHXLKCRNDFLEV (SEQ ID NO: 365). An additional embodiment is thepolynucleotides encoding these polypeptides.

[0208] This gene is expressed primarily in neutrophils.

[0209] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune orhematopoietic disorders, including inflammatory disorders, andallergies. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, haematopoetic, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0210] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product indicates a role inregulating the proliferation; survival; differentiation; and/oractivation of hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses).

[0211] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immunodeficiency diseases such as AIDS, leukemia,rheumatoid arthritis, granulomatous disease, inflammatory bowel disease,sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,such as T-cell mediated cytotoxicity; immune reactions to transplantedorgans and tissues, such as host-versus-graft and graft-versus-hostdiseases, or autoimmunity disorders, such as autoimmune infertility,lense tissue injury, demyelination, systemic lupus erythematosis, druginduced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,scleroderma and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0212] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:37 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 971 of SEQID NO:37, b is an integer of 15 to 985, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:37, and where bis greater than or equal to a+14.

[0213] Features of Protein Encoded by Gene No: 28

[0214] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: KADVKWHMCLQSPLCGLFCSIEGVLK (SEQ IDNO: 367),ACMNPAMCFVCACPHTGSTPEKAILQGRLISLGTSLSPASNGSGQQSFSICMINPSLPXSTSSHHLFSVLTGDLDSYSQRKLKPTSRKSFLLPKTQTYXVXHPSSPPLVLVQHRSPLSTYPKPVPSCCALDLISVIALETFLVYIHLFPSIDLSYWILSMLQPLLLIKQQSTKTLSLNCMLYSSYYLISFLSFKAKVLRRGGNILHHFFTSYSFFNTY(SEQ ID NO: 368), CPHTGSTPEKAILQGRLISLGTSLSPAS (SEQ ID NO: 369),QHRSPLSTYPKPVPSCCALDLISV (SEQ ID NO: 370), and/orIKQQSTKTLSLNCMLYSSYYLISFLSFKA (SEQ ID NO: 371). Polynucleotides encodingthese polypeptides are also encompassed by the invention.

[0215] This gene is expressed primarily in neutrophils.

[0216] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immuneand/or haematological disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., immune, hematopoietic and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0217] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 177 as residues: Pro-55 to Ser-66.

[0218] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product indicates a role inregulating the proliferation; survival; differentiation; and/oractivation of hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses).

[0219] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immunodeficiency diseases such as AIDS, leukemia,rheumatoid arthritis, granulomatous disease, inflammatory bowel disease,sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,such as T-cell mediated cytotoxicity; immune reactions to transplantedorgans and tissues, such as host-versus-graft and graft-versus-hostdiseases, or autoimmunity disorders, such as autoimmune infertility,lense tissue injury, demyelination, systemic lupus erythematosis, druginduced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,scleroderma and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0220] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:38 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1108 of SEQID NO:38, b is an integer of 15 to 1122, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:38, and whereb is greater than or equal to a+14.

[0221] Features of Protein Encoded by Gene No: 29

[0222] This gene is expressed primarily in neutrophils.

[0223] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immuneand haematological disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., immune, hematopoietic, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0224] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product indicates a role inregulating the proliferation; survival; differentiation; and/oractivation of hematopoietic cell lineages, including blood stem cells.This gene product may be involved in the regulation of cytokineproduction, antigen presentation, or other processes that may alsosuggest a usefulness in the treatment of cancer (e.g. by boosting immuneresponses).

[0225] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immunodeficiency diseases such as AIDS, leukemia,rheumatoid arthritis, granulomatous disease, inflammatory bowel disease,sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,such as T-cell mediated cytotoxicity; immune reactions to transplantedorgans and tissues, such as host-versus-graft and graft-versus-hostdiseases, or autoimmunity disorders, such as autoimmune infertility,lense tissue injury, demyelination, systemic lupus erythematosis, druginduced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,scleroderma and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0226] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:39 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 584 of SEQID NO:39, b is an integer of 15 to 598, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:39, and where bis greater than or equal to a+14.

[0227] Features of Protein Encoded by Gene No: 30

[0228] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: KYLVSSVLPTISMARSLISALRSG (SEQ ID NO:372). Polynucleotides encoding these polypeptides are also encompassedby the invention. The gene encoding the disclosed cDNA is believed toreside on chromosome 7. Accordingly, polynucleotides related to thisinvention are useful as a marker in linkage analysis for chromosome 7.

[0229] This gene is expressed primarily in ovarian cancer.

[0230] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive disorders, particularly ovarian cancer. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the reproductive system, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., reproductive, ovarian,and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0231] The tissue distribution in ovarian tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of ovarian cancer. Moreover, the protein isuseful for the treatment, detection, and/or prevention of endocrinedisorders, particularly those related to the reproductive system.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0232] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:40 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1115 of SEQID NO:40, b is an integer of 15 to 1129, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:40, and whereb is greater than or equal to a+14.

[0233] Features of Protein Encoded by Gene No: 31

[0234] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: MRTLFGAVRAPFSSLTLLLITPSPSPL (SEQ IDNO: 373), MAYAFHRTST (SEQ ID NO: 374), LKSTYTLLSILWFLVLIPVEGN (SEQ IDNO: 375), and/or GPLLASHATLCFSLGSKF (SEQ ID NO: 376). Polynucleotidesencoding these polypeptides are also encompassed by the invention.

[0235] This gene is expressed primarily in ovarian cancer.

[0236] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive, or endocrine disorders, particularly proliferativeconditions such as ovarian cancer. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the reproductive system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., reproductive, endocrine, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0237] The tissue distribution in ovarian tumor tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of ovarian cancer. Moreover, the protein isuseful for the detection, treatment, and/or prevention of a variety ofreproductive disorders such as infertility. In addition, the protein mayalso be useful in the development of novel or improved contraceptives.The expression within cellular sources marked by proliferating cellsindicates this protein may play a role in the regulation of cellulardivision, and may show utility in the diagnosis and treatment of cancerand other proliferative disorders. Similarly, developmental tissues relyon decisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0238] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:41 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1144 of SEQID NO:41, b is an integer of 15 to 1158, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:41, and whereb is greater than or equal to a+14.

[0239] Features of Protein Encoded by Gene No: 32

[0240] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: TVWGILPRKR (SEQ ID NO: 377).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0241] This gene is expressed primarily in ovarian tumor.

[0242] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive or endocrine disorders, particularly proliferativeconditions such as ovarian cancer. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the reproductive system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., reproductive, endocrine, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0243] The tissue distribution in ovarian tumor tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of ovarian cancer. Moreover, the protein isuseful for the detection, treatment, and/or prevention of a variety ofreproductive disorders such as infertility. In addition, the protein mayalso be useful in the development of novel or improved contraceptives.The expression within cellular sources marked by proliferating cellsindicates this protein may play a role in the regulation of cellulardivision, and may show utility in the diagnosis and treatment of cancerand other proliferative disorders. Similarly, developmental tissues relyon decisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0244] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:42 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1753 of SEQID NO:42, b is an integer of 15 to 1767, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:42, and whereb is greater than or equal to a+14.

[0245] Features of Protein Encoded by Gene No: 33

[0246] The translation product of this gene shares sequence homologywith uroplakin III which is thought to be important in urothelialdifferentiation (See Accession No. d10226610). In specific embodiments,polypeptides of the invention comprise the following amino acidsequence: ASIDTWPGRRSGGMIVITSI (SEQ ID NO: 378) and/orGSPQAETRWSDPIALHQGKSPASIDTWPGRRSGGMIVITSI (SEQ ID NO: 379).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0247] This gene is expressed primarily in ovarian tumor.

[0248] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive or endocrine disorders, particularly proliferativeconditions such as ovarian cancer. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the reproductive system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., reproductive, endocrine, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0249] The tissue distribution in ovarian tumor tissue, combined withthe homology to uroplakin III indicates that polynucleotides andpolypeptides corresponding to this gene are useful for the diagnosis andtreatment of reproductive disorders, urogential conditions, or endocrinedisorders. Moreover, the protein is useful for the detection, treatment,and/or prevention of a variety of reproductive disorders such asinfertility. In addition, the protein may also be useful in thedevelopment of novel or improved contraceptives. The expression withincellular sources marked by proliferating cells indicates this proteinmay play a role in the regulation of cellular division, and may showutility in the diagnosis and treatment of cancer and other proliferativedisorders. Similarly, developmental tissues rely on decisions involvingcell differentiation and/or apoptosis in pattern formation. Thus thisprotein may also be involved in apoptosis or tissue differentiation andcould again be useful in cancer therapy. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0250] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:43 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 903 of SEQID NO:43, b is an integer of 15 to 917, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:43, and where bis greater than or equal to a+14.

[0251] Features of Protein Encoded by Gene No: 34

[0252] The translation product of this gene shares sequence homologywith estrogen-responsive finger protein, which is thought to beimportant in uterine implantation. (See Accession No. 1088467; and J.Biol. Chem. 270 (41), 24406-24413 (1995), herein incorporated byreference in its entirety.) Moreover, the protein product of this genewas also shown to homology to the human rfp transforming protein (SeeGenbank Accession No. gi|337372) which is thought to play a role in inmale germ cell development. Preferred polypeptide fragments comprise theamino acid sequence: VXDITFDPDTAHKYLRLQEENRKVTNTTPWEHPYPDLPSRFLH (SEQ IDNO: 380); LYLHRYYFEVEIFGAGTYV (SEQ ID NO: 381); SCISGNNFSWSLQWNGKEFTAW(SEQ ID NO: 382); TPLKAGPFWSSGSILTS (SEQ ID NO: 383);SVSEVKAVAEMQFGELLAAVRKAQANVMLFLXEKEQAAL (SEQ ID NO: 384);EKSKQELETMAAISNTVQFLEEYCKFKINTEDITFPSVYIGLKD (SEQ ID NO: 385);LENYKKKLQEFSKEEEYDIRTQVSAXVQR (SEQ ID NO: 386); GTVSRERRAG (SEQ ID NO:388),HGDPTQSWPFLELGVYIDFPGGILSFYGVEYDSMTLVHKFACKFSEPVYAAFWLSKKENAIRIVDLGEEPEKPAPSLVGTAP (SEQ ID NO: 389), SFYGVEYDSMTLVHKFACKFSEPVYAAFWL (SEQ ID NO:390),AELQCTQLDLERKLKLNENAISRLQANQKSVLVSVSEVKAVAEMQFGELLAAVRKAQANVMLFLXEKEQAALSQANGIKAHLEYKSAEMEKSKQELETMAAISNTVQFLEEYCKFKNTEDITFPSVYIGLKDKLSGIRKVITESTVHLIXXLENYKKKLQEFSKEEEYDIRTQVSAXVQRKYWTSKPEPSTREQFLQYVXDITFDPDTAHKYLRLQEENRKVTNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTYVGLTCKGIDXKGEERXSCISGNNFSWSLQWNGKEFTAWYSDMETPLKAGPFWSSGSILTSQEGSFPSMA(SEQ ID NO: 391),RTAPYGAKESSWRMFSFRDPIGFQKPATISSYFCPQITLKCKSHHCSWQRSGIWLLESREQSPPRTVLASRVPLPDLQSGWRFPSWKARRQHRLVLKTCRQTCEPESWNHTLRHRRKGSLLGSQYRPRAPERASFEWGLHVTVPGRELLPVPLEAPGEVVSGNATXALLPFXVDAFAGQANIGACPEDLHLKIVPVQVQTLLGQHLPPVQEPAGEVRVGMLPGRGVGDLAVLLLQPEILVCCVRVERDVXHILEELFPGAGLRFGSPIFALNNGRHLSSDVILLFLGKLLELFLIVLQXXD(SEQ ID NO: 392), and/or GVYIDFPGGILSFYGVEYDSMTLVHKFACKFSEPVYAA (SEQ IDNO: 387). Also preferred are polynucleotide fragments encoding thesepolypeptide fragments.

[0253] This gene is expressed primarily in ovarian cancer.

[0254] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, ovariancancer and other disorders of the reproductive system. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the reproductive system, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., reproductive,developmental, ovarian, testicular, and cancerous and wounded tissues)or bodily fluids (e.g., lymph, seminal fluid, amniotic fluid, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0255] The tissue distribution in ovarian tumors, combined with thehomology to estrogen-responsive finger protein, in addition, to theconserved rfp transforming protein indicates that polynucleotides andpolypeptides corresponding to this gene are useful for diagnosis andtreatment of ovarian cancer and other disorders of the reproductivesystem. Moreover, the expression within cellular sources marked byproliferating cells indicates this protein may play a role in theregulation of cellular division, and may show utility in the diagnosisand treatment of cancer and other proliferative disorders. Similarly,developmental tissues rely on decisions involving cell differentiationand/or apoptosis in pattern formation. Thus this protein may also beinvolved in apoptosis or tissue differentiation and could again beuseful in cancer therapy. The protein may also show utility in thedevelopment of novel contraceptives. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0256] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:44 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1973 of SEQID NO:44, b is an integer of 15 to 1987, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:44, and whereb is greater than or equal to a+14.

[0257] Features of Protein Encoded by Gene No: 35

[0258] This gene shows sequence homology to a Caenorhabditis elegansgene, called D1054.3, in addition, to the Sgt1p protein of Saccharomycescerevisiae which are thought to play a role in the regulation ofcellular division and developmental precesses (See Accession Nos.gn1|PID|e348554 and gi|1870791, respectively) Preferred polypeptidefragments comprise the amino acid sequence:SKIKYDWYQTESQVVITLMIKNVQKNDVNVEFSEKELSALVKLPSGEDYNLKLELLHPIIPEQSTFKVLSTKIEIKLKKPEAVRWEKLEGQGDVPTPKQFVADVKNLYPSSSPYTRNWDKLVGEIKEEEKNEKLEGDAALNRLFQQIYSDGSDEVKRAMNKSFMESGGTVLSTNWSDVGKRKVEINPPDDMEWKKY(SEQ ID NO: 393); GDAALNRLFQQIYSDGSDEVKRAMNKSFMESGGTVLSTN (SEQ ID NO:394);MAAAAAGTXXSQRFFQSFSDALIDEDPQAALEELTKALEQKPDDAQYYCQRAYCHILLGNYCVAVADAKKSLELNPNNSTAMLRKGICEYHEKNYAAALETFTEGQKLDSADANFSVWIKRCQEAQNGSESEVVSPKFSFFMFLLF (SEQ ID NO: 396), LEELTKALEQKPDDAQYYCQRAYCHILLGNYCVAVADA (SEQ ID NO: 397),AMLRKGICEYHEKiNYAAALETFTEGQKLDSA (SEQ ID NO: 398), LRLWNRNQMMHSIIVKELIVTFFLGITVLLLLMQRSL (SEQ ID NO: 399), NSIQIIPLLC (SEQ ID NO:400),YMHFNNTVAKLTCKNLSLSTYQNQSASQWTHQSKIKYDWYQTESQVVITLMIKNVQKNDVNVEFSEKELSALVKLPSGEDYNLKLELLHPIIPEQSTFKVLSTKIEIKLKKPEAVRWEKLEGQGDVPTPKQFVADVKNLYPSSSPYTRNWDKLVGEIKEEEKNEKLEGDAALNRLFQQIYSDGSDEVKRAMNKSFMESGGTVLSTNWSDVGKRKVEINPPDDMEWKKY(SEQ ID NO: 401), TCKNLSLSTYQNQSASQWTHQSKIKYDWY (SEQ ID NO: 402),EKELSALVKLPSGEDYNLKLELLH (SEQ ID NO: 403), LHPIIPEQSTFKVLSTKIEIKLKKPEAVR(SEQ ID NO: 404), KQFVADVKNLYPSSSPYTRNWDKL (SEQ ID NO: 405), and/orDWYQTESQVVITLMIKNVQKNDV (SEQ ID NO: 395). Also preferred arepolynucleotide fragments encoding these polypeptide fragments

[0259] This gene is expressed primarily in osteoclastoma.

[0260] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, skeletalor developmental disorders, particularly osteoclastoma and other formsof cancer. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theskeletal system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., skeletal, developmental, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0261] The tissue distribution in osteoclastoma, combined with thehomology to the D1054.3 and Sgt1p proteins indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and treatment of osteoclastoma and other forms of cancers.Moreover, the expression within embryonic tissue and other cellularsources marked by proliferating cells indicates this protein may play arole in the regulation of cellular division, and may show utility in thediagnosis and treatment of cancer and other proliferative disorders.Similarly, developmental tissues rely on decisions involving celldifferentiation and/or apoptosis in pattern formation. Thus this proteinmay also be involved in apoptosis or tissue differentiation and couldagain be useful in cancer therapy. Protein may also play a role as atumor supressor, or in the development of tumor progression inhibitors.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0262] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:45 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 2039 of SEQID NO:45, b is an integer of 15 to 2053, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:45, and whereb is greater than or equal to a+14.

[0263] Features of Protein Encoded by Gene No: 36

[0264] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: GSKGQERKWRVRMGYLN (SEQ ID NO: 406),QRYRLLPLFCYVCSRKIKLNENLFVFSAYSLATLPHTYLFSIVEC SSFCLSGTRN (SEQ ID NO:407), and/or FSAYSLATLPHTYLFSIVEC SSFCLSG (SEQ ID NO: 408).Polynucleotides encoding these polypeptides are also encompassed by theinvention. The gene encoding the disclosed cDNA is believed to reside onchromosome 7. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 7.

[0265] This gene is expressed primarily in human placenta.

[0266] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,developmental, vascular, and/or reproductive disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the embryonic and reproductivesystems, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,developmental, vascular, reproductive, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, amniotic fluid,urine, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0267] The tissue distribution in human placenta tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of the disorders of embryonic andreproductive systems. Moreover, the protein is useful for the detection,treatment, and/or prevention of a variety of vascular disorders, whichinclude, but are not limited to, microvascular disease, aneurysm,arteriosclerosis, atherosclerosis, stroke, or embolism. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0268] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:46 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1258 of SEQID NO:46, b is an integer of 15 to 1272, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:46, and whereb is greater than or equal to a+14.

[0269] Features of Protein Encoded by Gene No: 37

[0270] This gene is expressed primarily in anergic T-cells.

[0271] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune orhematopoietic disorders, particularly inflammatory conditions andimmunodeficiencies such as AIDS. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., immune, hematopoietic, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0272] The tissue distribution in anergic T-cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of T cell related disorders. Moreover,the expression of this gene product indicates a role in regulating theproliferation; survival; differentiation; and/or activation ofhematopoietic cell lineages, including blood stem cells. This geneproduct may be involved in the regulation of cytokine production,antigen presentation, or other processes that may also suggest ausefulness in the treatment of cancer (e.g. by boosting immuneresponses).

[0273] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immunodeficiency diseases such as AIDS, leukemia,rheumatoid arthritis, granulomatous disease, inflammatory bowel disease,sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities,such as T-cell mediated cytotoxicity; immune reactions to transplantedorgans and tissues, such as host-versus-graft and graft-versus-hostdiseases, or autoimmunity disorders, such as autoimmune infertility,lense tissue injury, demyelination, systemic lupus erythematosis, druginduced hemolytic anemia, rheumatoid arthritis, Sjogren's disease,scleroderma and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0274] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:47 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 759 of SEQID NO:47, b is an integer of 15 to 773, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:47, and where bis greater than or equal to a+14.

[0275] Features of Protein Encoded by Gene No: 38

[0276] The translation product of this gene shares sequence homologywith a murine bone-related sulphatase (See Genbank Accession No.3046314, and Genseq Accession No. R51355) which is thought to beinvolved in proteoglycan metabolism. In specific embodiments,polypeptides of the invention comprise the following amino acidsequence: ASFGSCSLSLPCSARERTPEGGGWPGGRLSEPLPA (SEQ ID NO: 409), APNVVLV(SEQ ID NO: 410), DGRLTF (SEQ ID NO: 411), PGSQVVKLPFINFM (SEQ ID NO:412), FLNAYTNSP (SEQ ID NO: 413), ICCPSRAAMWSGLFTHLTESWNNFKGLDPNYTTWMD(SEQ ID NO: 414), TQKFGK (SEQ ID NO: 415), DYTSGHHSI (SEQ ID NO: 416),SNRVEAWTRDVAFLLRQEGRP (SEQ ID NO: 417), DWQNTDKA (SEQ ID NO: 418),YLGLNLPHPYPSPSSGENFGSSTFHTSLYWLEKV (SEQ ID NO: 419), DAIKIPKW (SEQ IDNO: 420), YTKNCTG (SEQ ID NO: 421), NIRAFYYAMCAETDAMLGEILALH (SEQ ID NO:422), LDLLQKTIVIY (SEQ ID NO: 423), MEHRQFYKMSMYEAS (SEQ ID NO: 424),HVPLLMMGPGIKA (SEQ ID NO: 425), VVSLVDIYPTMLDIAGI (SEQ ID NO: 426),DPDELTN (SEQ ID NO:427), WKYIAY (SEQ ID NO: 428),NFPEITYSLDQKLHSIINYPKVSASVHQYNKEQFIKWKQSIGQNYSNVIANFRWHQDWQKEPRKYENAIDQWLKTHMNPRAV(SEQ ID NO: 429), FPEITYSLDQKL (SEQ ID NO:430), NYPKVSASVHQYNKEQFI (SEQID NO: 431), GQNYSNVIA (SEQ ID NO: 432), RWHQDWQ (SEQ ID NO: 433),and/or PRKYENAI (SEQ ID NO: 434). Polynucleotides encoding thesepolypeptides are also encompassed by the invention.

[0277] This gene is expressed primarily in retina.

[0278] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, visual,skeletal, or metabolic disorders, particularly eye dieases and bonemetabolic disorders. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theeye, expression of this gene at significantly higher or lower levels maybe routinely detected in certain tissues or cell types (e.g., visual,skeletal, metabolic, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, vitreous humor, aqueous humor,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0279] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 187 as residues: Ala-21 to Arg-27, Asp-40 to Arg-45, Glu-97to Thr-110, Glu-117 to Lys-128, Arg-175 to Lys-182, Pro-207 to Gly-220,Val-253 to Ile-272.

[0280] The tissue distribution in retina, combined with the homology tosulphatases indicates that polynucleotides and polypeptidescorresponding to this gene are useful for diagnosis and treatment of eyedisorders. Moreover, this gene may be useful in the detection,treatment, and/or prevention of bone-related disorders, osteoporosis,Paget's disease, osteomalacia, in addition to bone metabolic disorders,particularly those involving proteoglycans. The protein is also usefulin the disorders involving aberrant proteoglycan metabolism or relatedconditions, which may include arthritis, immune cell migration, cellularproliferation, vascular disorders, hematopoietic disorders, in additionto showing utility in the detection, treatment, and/or prevention of thedisorders mentioned above. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0281] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:48 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 2105 of SEQID NO:48, b is an integer of 15 to 2119, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:48, and whereb is greater than or equal to a+14.

[0282] Features of Protein Encoded by Gene No: 39

[0283] This gene is expressed primarily in human stomach cancers.

[0284] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,gastointestinal disorders, particularly cancer. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the cancer, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., endothelial, gastrointestinal, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,chyme, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0285] The tissue distribution in tumors of the stomach indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of these tumors, inaddition to other tumors in other tissues. The protein may also beuseful for the treatment and/or prevention of ulcers, in addition toadditional gastrointestinal or metabolic conditions. Protein, as wellas, antibodies directed against the protein may show utility as atissue-specific marker and/or immunotherapy target for the above listedtissues.

[0286] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:49 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1174 of SEQID NO:49, b is an integer of 15 to 1188, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:49, and whereb is greater than or equal to a+14.,

[0287] Features of Protein Encoded by Gene No: 40

[0288] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: RNSLHCYNEQPPNASGLIQWSSD LIPISLQCGCSW(SEQ ID NO: 435). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0289] This gene is expressed primarily in human synovial membrane.

[0290] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof synovial membrane, skeletal and/or musculoskeletal disorders.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the synovialmembrane system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., skeletal, muscular, rheumatiod, synovial, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0291] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 189 as residues: Pro-10 to Ser-20.

[0292] The tissue distribution in synovial tissue indicates the productof this gene may play a role in the detection, treatment, and/orprevention of disorders and conditions affecting the skeletalsystemskeletal system, in particular osteoporosis, bone cancer, as wellas, disorders afflicting connective tissues (e.g. arthritis, trauma,tendonitis, chrondomalacia and inflammation), such as in the diagnosisor treatment of various autoimmune disorders such as rheumatoidarthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism,spinal deformation, and specific joint abnormalities as well aschondrodysplasias (i.e. spondyloepiphyseal dysplasia congenital familialosteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasiatype Schmid). Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0293] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:50 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 464 of SEQID NO:50, b is an integer of 15 to 478, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:50, and where bis greater than or equal to a+14.

[0294] Features of Protein Encoded by Gene No: 41

[0295] The translation product of this gene shares sequence homologywith adipose specific collagen-like factor as well as the humanadipocyte complement related protein Acrp30, the latter of which isknown to be important in energy balance and homeostasis involving foodintake, particularly in carbohydrate and lipid catabolism/anabolism (SeeGenbank Accession Nos.gnl|PID|d1008822 and W09108, respectively). Oneembodiment of this gene comprises polypeptides of the following aminoacid sequence:XLWDPGLPGVCRCGSIVLKSAFSVGITTSYPEXRLPIIFNKVLLPRGXALQPCHRGSSSVLSQGIYYFSYDITLANKHLAIGLVHNGQYRIKTFDANTGNHDVASGSTVIYLQPEDEVWLEIFFTDQNGLFSDPGWADSLFSGFLLYVDTDYLDSISEDDEL(SEQ ID NO: 436), GSIVLKSAFSVGITT (SEQ ID NO: 437), GIYYFSYDITLANK (SEQID NO: 438), DSLFSGFLLYVDT (SEQ ID NO: 439), and/or NHDVASGSTVIYL (SEQID NO: 440). An additional embodiment is the polynucleotides encodingthese polypeptides.

[0296] This gene is expressed primarily in human schwanoma.

[0297] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, neural orintegumentary disorders, particularly neurofibroma. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the diseases relating to peripheral orsympathetic nervous system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., neural, integumentary, extracellular matrix, cancerousand wounded tissues) or bodily fluids (e.g., lymph, serum, plasma,urine, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0298] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 190 as residues: Gly-16 to Pro-30, Pro-42 to Gly-56, Gly-62to Gly-77, Glu-93 to Gly-104, Glu-109 to Glu-114, Pro-121 to Asp-126.

[0299] The tissue distribution in schwanoma cells combined with thehomology to a conserved human adipose specific collagen-like factor aswell as to the human adipocyte complement related protein Acrp30,indicates that polynucleotides and polypeptides corresponding to thisgene are useful for the detection/treatment of neurodegenerative diseasestates and behavioural disorders particularly neuroschwannoma, andincluding Alzheimers Disease, Parkinsons Disease, Huntingtons Disease,Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessivecompulsive disorder, panic disorder, learning disabilities, ALS,psychoses , autism, and altered behaviors, including disorders infeeding, sleep patterns, balance, and perception. In addition, the geneor gene product may also play a role in the treatment and/or detectionof developmental disorders associated with the developing embryo,sexually-linked disorders, or disorders of the cardiovascular system.

[0300] Moreover, polynucleotides and polypeptides corresponding to thisgene are useful for the treatment, diagnosis, and/or prevention ofvarious skin disorders including congenital disorders (i.e. nevi, moles,freckles, Mongolian spots, hemangiomas, port-wine syndrome),integumentary tumors (i.e. keratoses, Bowen's disease, basal cellcarcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease,mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation ofthe skin (i.e.wounds, rashes, prickly heat disorder, psoriasis,dermatitis), atherosclerosis, uticaria, eczema, photosensitivity,autoimmune disorders (i.e. lupus erythematosus, vitiligo,dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus),keloids, striae, erythema, petechiae, purpura, and xanthelasma. Inaddition, such disorders may predispose increased susceptibility toviral and bacterial infections of the skin (i.e. cold sores, warts,chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis,erysipelas, impetigo, tinea, althletes foot, and ringworm). Moreover,the protein product of this gene may also be useful for the treatment ordiagnosis of various connective tissue disorders such as arthritis,trauma, tendonitis, chrondomalacia and inflammation, autoimmunedisorders such as rheumatoid arthritis, lupus, scleroderma, anddermatomyositis as well as dwarfism, spinal deformation, and specificjoint abnormalities as well as chondrodysplasias (i.e.spondyloepiphyseal dysplasia congenita, familial osteoarthritis,Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).

[0301] Alternatively, considering the homology to a conserved adiposespecific collagen-like factor, would suggest that this protein may alsobe important in the diagnosis or treatment of various autoimmunedisorders such as rheumatoid arthritis, lupus, scleroderma, anddermatomyositis as well as dwarfism, spinal deformation, and specificjoint abnormalities as well as chondrodysplasias ie. spondyloepiphysealdysplasia congenita, familial osteoarthritis, Atelosteogenesis type II,metaphyseal chondrodysplasia type Schmid. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0302] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:51 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1319 of SEQID NO:51, b is an integer of 15 to 1333, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:51, and whereb is greater than or equal to a+14.

[0303] Features of Protein Encoded by Gene No: 42

[0304] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: SNSHTHTHVKSFLR (SEQ ID NO: 441).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0305] This gene is expressed primarily in human activated T-Cells.

[0306] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,inmmunodeficiencies, inflammatory conditions, and other immune orhematopoietic disorders. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thedisorders of the immune system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., immune, hematopoietic, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0307] The tissue distribution in T-cells indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thediagnosis, treatment, and/or prevention of a variety of immune systemdisorders. Expression of this gene product in T-cells indicates a rolein the regulation of the proliferation; survival; differentiation;and/or activation of potentially all hematopoietic cell lineages,including blood stem cells. This gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g., by boosting immune responses).

[0308] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, andleukemia. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tumors and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0309] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:52 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1241 of SEQID NO:52, b is an integer of 15 to 1255, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:52, and whereb is greater than or equal to a+14.

[0310] Features of Protein Encoded by Gene No: 43

[0311] The protein product of this gene was found to have homology tothe human CD84 protein which, as a novel member of the Ig superfamily,is thought to play an important role in the modulation of the immuneresponse. The present invention appears to encode a novel full-lengthCD84 homolog and is highly enriched, if not specific, for activated Tcells. In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: ITPLGLGAAD (SEQ ID NO: 442),TLRVLGKVPAVCPWCALWRKAGMDMTYSWLSRGDSTYTFHEGPVLSTSWRPGDSALSYTCRANNPISNVSSCPIPDGPFYADPNYASEKPSTAFCLLAKGLLIFLLLVILAMGLWVIRVQKRHKMPRMKKLMRNRMKLRKEAKPGSSPA(SEQ ID NO: 443), AVCPWCALWRKAGMDMTYSWL (SEQ ID NO: 444),PGDSALSYTCRANNPISNVSSCPI (SEQ ID NO: 445), YASEKPSTAFCLLAKGLLIFLLLV (SEQID NO: 446), and/or QKRHKMPRMKKLMRNRMKLRKEAKPG (SEQ ID NO: 447).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0312] This gene is expressed primarily in human activated T-Cells.

[0313] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,immunodeficiencies, inflammatory conditions, infections, and otherimmune or hematopoietic disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the disorders of the immune system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., immune, hematopoietic, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0314] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 192 as residues: Glu-15 to Arg-23, Asn-79 to Gly-84.

[0315] The tissue distribution in activated T-cells indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product in T-cells indicates arole in the regulation of the proliferation; survival; differentiation;and/or activation of potentially all hematopoietic cell lineages,including blood stem cells. This gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g., by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the natural gene product may be involved inimmune functions. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, and leukemia. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tumors and tissues. Inaddition, this gene product may have commercial utility in the expansionof stem cells and committed progenitors of various blood lineages, andin the differentiation and/or proliferation of various cell types.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0316] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID.NO:53 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1126 of SEQID NO:53, b is an integer of 15 to 1140, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:53, and whereb is greater than or equal to a+14.

[0317] Features of Protein Encoded by Gene No: 44

[0318] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: IAWSGNIPSLLCLFEHDMSFQDE (SEQ ID NO:448). Polynucleotides encoding these polypeptides are also encompassedby the invention.

[0319] This gene is expressed primarily in human tonsil.

[0320] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,inflammatory conditions, infections, or immunodeficiencies, and immuneor hematopoietic diseases and/or disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune diseases, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, hematopoietic, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0321] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 193 as residues: Ile-2 to Lys-9, Gln-43 to Phe-49, Asn-59 toHis-69, Gly-87 to Asp-93.

[0322] The tissue distribution in tonsils indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thediagnosis, treatment, and/or prevention of a variety of immune systemdisorders. Expression of this gene product indicates a role in theregulation of the proliferation; survival; differentiation; and/oractivation of potentially all hematopoietic cell lineages, includingblood stem cells. This gene product may be involved in the regulation ofcytokine production, antigen presentation, or other processes that mayalso suggest a usefulness in the treatment of cancer (e.g., by boostingimmune responses).

[0323] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, andleukemia. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tumors and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0324] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:54 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1206 of SEQID NO:54, b is an integer of 15 to 1220, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:54, and whereb is greater than or equal to a+14.

[0325] Features of Protein Encoded by Gene No: 45

[0326] The translation product of this gene shares sequence homologywith a novel human G52-24 secreted protein as well as the earlylymphocyte activation antigen CD69, the latter of which has been shownto be important in lymphocyte proliferation and functions as a signaltransmitting receptor in lymphocytes, natural killer cells, andplatelets (See Genseq and Genbank Accession Nos. W27288 and gi|558352,respectively). Preferred polypeptides comprise the following amino acidsequence: ENFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQLVMKEDGANLYVAKVSQVPRMNPXLSWVLLCYPGWSAVXTIVAHCSLDFPGSK (SEQ ID NO: 449),ELTAIKSHQYVLQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELVRK (SEQ IDNO: 450), WIGLSREQGQPWKWING (SEQ ID NO: 451), CPESWIGFQRKC (SEQ ID NO:452), NFLLRYKGPSDHWIGL (SEQ ID NO: 453),ASHLRLLSSWDYRFPILGAGECAYLNDKGASSARHYTERKWI CSKSDIHV (SEQ ID NO: 454),ENFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQLVMKEDGANLYVAKVSQVPRMNPXLSWVLLCYPGWSAVXTIVAHCSLDFPGSK (SEQ ID NO: 455),EQLEELELKKKDFIKILESVQGNWRQNEDSGKGPQRSCL (SEQ ID NO: 457),FWPESKIQPYKDMFSCEII (SEQ ID NO: 458),SWTSSLLNXCLHSKEHSIKATIWRLFFXILTIILCGMVAALSAIRANCHQEPSVCSSSCMPRKLDWFSKKVFLFF (SEQ ID NO: 456),EQLEELELKKKDFIKILESVQGNWRQNEDSGKGPQRSCLHSKEHSIKATLIWRLFFLI (SEQ ID NO:459), and/or ENFLLRYKGPSDHWIGLXXEQGQPWKWINGTEWTRQ (SEQ ID NO: 460). Alsopreferred are the polynucleotides encoding these polypeptides.

[0327] This gene is expressed primarily in human testes.

[0328] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive, endocrine, and/or immune or hematopoietic disorders.Similarly, polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of the disordersof reproductive system, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g., immune, reproductive, endcrine, cancerous and woundedtissues) or bodily fluids (e.g., lymph, seminal fluid, serum, plasma,urine, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0329] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 194 as residues: Asn-20 to Pro-25, Ser-48 to Asp-65.

[0330] The tissue distribution in human testes indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety ofreproductive disorders, particularly autoimmune disorders, infertility,or the protein may even be useful as a novel contraceptive. Homology ofthis gene product to the early lymphocyte activation antigen CD69indicates a role in the regulation of the proliferation; survival;differentiation; and/or activation of potentially all hematopoietic celllineages, including blood stem cells. This gene product may be involvedin the regulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g., by boosting immune responses).

[0331] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, andleukemia. In addition, this gene product may have commercial utility inthe expansion of stem cells and comemitted progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0332] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:55 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 680 of SEQID NO:55, b is an integer of 15 to 694, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:55, and where bis greater than or equal to a+14.

[0333] Features of Protein Encoded by Gene No: 46

[0334] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: RHEPDPM (SEQ ID NO: 461).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0335] This gene is expressed primarily in human testes.

[0336] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, malereproductive or endocrine disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the reproductive system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., endocrine, reproductive, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, seminalfluid, serum, plasma, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0337] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 195 as residues: Pro-20 to Trp-25, Arg-33 to Thr-38, Asn-51to Ile-56, Gly-82 to Ser-91, Lys-151 to Arg-156.

[0338] The tissue distribution in human testicular tissues and cellsindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the detection, treatment, and/or prevention ofvarious endocrine disorders and cancers, particularly Addison's disease,Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g.,diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-,hypopituitarism), thyroid (e.g., hyper-, hypothyroidism), parathyroid(e.g., hyper-, hypoparathyroidism) , hypothallamus, and testes.

[0339] Alternatively, expression within the human testis may beindicative for a role in normal testicular function, and may implicatethis gene product in male fertility, and could even suggest its use as anovel contraceptive. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0340] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:56 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 974 of SEQID NO:56, b is an integer of 15 to 988, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:56, and where bis greater than or equal to a+14.

[0341] Features of Protein Encoded by Gene No: 47

[0342] One embodiment of this gene comprises polypeptides of thefollowing amino acid sequence:LKGREAGAGPGTAGAPGREDANGXXRGRGGXHQLYLWVDNIPLSRPKRNLSRDFSDGVLVAEVIKFYFPKiMVEMHNYVGTSSLQQKLSNWGHLNRKVLKRLNFSVPDDV(SEQ ID NO: 462), WVDNIPLSRPKRNLSRDFSDGVLVA (SEQ ID NO: 463),YVGTSSLQQKLSNWGHLNRKVLKRL (SEQ ID NO: 464),GSAWRRGRGAGSRAPAPYRSWLPRMAVATWMWVYPRRPEVKVSRTPREGVSSAGTGRRRLGLQRITGRCRATPASSSRSLKRSRSCWPLKRPCRSCR (SEQ ID NO: 465), WLPRMAVATWIMWVYPRRPEVK (SEQ ID NO:466), CRATPASSSRSLKRSRSCWPLKR (SEQ ID NO: 467),EHNTDFNGAALSRNLQTFRLSTPCARREGRLLRAHRRCPPYSWRSHASPLPLQLLRSPSPRWVPGKLPGGAGEPLSGPGQIPPWLRAWGTSLDGDAAVLGAGRGPDSGGVDRAKGPPPKAQRREMQGRAQGVGHCFGGQARSLHVASGLWKAVHSPDPDLRSGRRRLSPGPALLEFLSHLLHAHPSQGRRALGPQQARESSGLRPPNGLSIGGWVRRGVGALAGTRASPRGPGRRSPLLTXRXLEPPGEVFDPHILELEQVLQAPYLHLQDLHGLLRGQQLLLLFSDLEDEAGVALQRPVIRWRPRRRRPVPAELTPSLGVRDTFfSGLLGYTHIHVATAILGSQLL (SEQ ID NO: 468); TDFNGAALSRNLQTFRLSTPCARREG (SEQ ID NO: 469),RCPPYSWRSHASPLPLQLLRSPSPR (SEQ ID NO: 470), GAGEPLSGPGQIPPWLRAWGTSLD(SEQ ID NO: 471), LGAGRGPDSGGVDRAKGPPPKAQRREMQGR (SEQ ID NO: 472),QARSLHVASGLWKAVHSPDPDLR (SEQ ID NO: 473), HPSQ GRRALGPQQARESSGL (SEQ IDNO: 474), IGGWVRRGVGALAGTRASPRGPGRRSP (SEQ ID NO: 475),EPPGEVFDPHILELEQVLQAPYLHL (SEQ ID NO: 476), and/orVPAELTPSLGVRDTFTSGLLGYTHIHVA (SEQ ID NO: 477). An additional embodimentis the polynucleotides encoding these polypeptides.

[0343] This gene is expressed primarily in human adult testis.

[0344] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,reproductive and/or endocrine disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the disorders of the reproductive system, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., reproductive,endocrine, cancerous and wounded tissues) or bodily fluids (e.g., lymph,seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0345] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 196 as residues: Gln-21 to Gly-33, Gln-55 to Glu-60.

[0346] The tissue distribution in testicular tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection, treatment, and/or prevention of reproductive systemdisorders, and may be indicative of a role for this gene product innormal testicular function, male fertility, and/or as a malecontraceptive. Protein, as well as, antibodies directed against theprotein may show utility as a tissue-specific marker and/orimmunotherapy target for the above listed tissues.

[0347] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:57 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1486 of SEQID NO:57, b is an integer of 15 to 1500, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:57, and whereb is greater than or equal to a+14.

[0348] Features of Protein Encoded by Gene No: 48

[0349] The translation product of this gene shares sequence homologywith the human M phase phosphoprotein 10 as well as ORF YJR002w ofSaccharomyces cerevisiae (See Genbank Accession No.gn1|PID|e266673)which are thought to play important roles in the regulation of cellulardivision. Preferred polypeptides comprise the following amino acidsequence:AKNSQKEENPEHVEIQKMMDSLFLKLDALSNFHFIPKPPVPEIKVVSNLPAITMEEVAPVSVSDAALLAPEEIKEKNKAGDIKTAAEKTATDKKRERRKKKYQKRMKIKEKEKRRKLLEKSSVDQAGKYSKTVASEKLKQLTKTGKASFIKVRTRERKLLKGTFVGEVDSKCWVTGMSEPADSPPVG(SEQ ID NO: 478), LQDEGKDKALKSSQAFFSKLQDQVKiMQINDAKKTEKKKKKRQDISVHKLKL(SEQ ID NO: 479), DEGKDKALKSSQAFFSKLQDQVKMQINDA (SEQ ID NO: 480),EENPEHVEIQKMMDSLFLKLDALSNFHF (SEQ ID NO: 481),SSVDQAGKYSKTVASEKLKQLTKTGKASFIK (SEQ ID NO: 483),VSVSDAALLAPEEIKEKNKAGDI (SEQ ID NO: 484), VLEVMVTVAPK (SEQ ID NO: 485),LQDEGKDKALKSSQAFFSKLQDQVKMQINDAKKTE (SEQ ID NO: 486), and/orSNLPAITMEEVAP (SEQ ID NO: 482). Also preferred are the polynucleotidesencoding these polypeptides.

[0350] This gene is expressed primarily in human thyroid.

[0351] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,endocrine, proliferative, or developmental disorders, particularlydiseases relating to the thyroid gland, particularly hyper- andhypothyroidism. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thedisorders of the endocrine system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., endocrine, developmental,metabolic, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0352] The tissue distribution in human thyroid indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor metabolic disorders, particularly hyper-, hypothyroidism, Graves'disease, Hashimoto's thyroiditis, and/or cancer or neoplasias of thethyroid, and/or other endocrine organs and immune system. Moreover, theprotein may show utility in the diagnosis, prevention, and/or treatmentof developmental disorders. In addition, the homology to an M phasephosphoprotein indicates it may be a key player in the proliferation,maintenance, and/or differentiation of various cell types duringdevelopment. It may also act as a morphogen to control cell and tissuetype specification. Because of potential roles in proliferation anddifferentiation, this gene product may have applications in the adultfor tissue regeneration and the treatment of cancers. Protein, as wellas, antibodies directed against the protein may show utility as atissue-specific marker and/or immunotherapy target for the above listedtissues.

[0353] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:58 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1377 of SEQID NO:58, b is an integer of 15 to 1391. where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:58, and whereb is greater than or equal to a+14.

[0354] Features of Protein Encoded by Gene No: 49

[0355] The translation product of this gene was found to have homologyto the cell division control protein 48 (cdc48) of Methanococcusjannaschii (See Genbank Accession No.gi|1591785) which is thought toplay a key role in the regulation of cellular division. In specificembodiments, polypeptides of the invention comprise the following aminoacid sequence: HEAAQGAVCRGQGAPATNPQAPVAAAARVARRVN (SEQ ID NO: 487), KIPSANRRATRCLGCDHQNFVKVRNKHKGKPTFMEEVLEHLPGKTQDEVQQHEKWYQKFLALEERKKESIQIWKTKKQQKREEIFKLKEKADNTPVLFHNKQEDNQKQKEEQRkKQKLAVEAWKKQKSIEMSMKCASQLKKKKKKKKKNQKERQRQFKLKLLLESYTQQKKEQEEFLRLEKEIREKAEKAEKRKNAADEISRFQERDLHKLELKILDRQAKEDEKSQKQRRLAKLKEKVENNVSRDPSRLYKPTK(SEQ ID NO: 488), VKVRNKHKGKPTFMEEVLEHLPGK (SEQ ID NO: 489),QHEKWYQKFLALEERKKESIQIW (SEQ ID NO: 490),FKLKEKADNTPVLFHNKQEDNQKQKEEQRKK (SEQ ID NO: 491),FLRLEKEIREKAEKAEKRKNAADEISRFQERDLHKL (SEQ ID NO: 492), and/orKQRRLAKLKEKVENNVSRDPSRLY (SEQ ID NO: 493). Polynucleotides encodingthese polypeptides are also encompassed by the invention.

[0356] This gene is expressed primarily in pancreas, and to a lesserextent in kidney and bone marrow.

[0357] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, pancreas,urogenital, developmental, metabolic, immune, and/or hematopoieticdisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thepancreas, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,endocrine, developmental, metabolic, immune, hematopoietic,gastrointestinal, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, bile, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0358] Preferred epitopes include those comprising a sequence shown inSEQ ID NO:198 as residues: Pro-35 to Cys-43, Gln-56 to Lys-67, Thr-73 toLys-78, Tyr-93 to Asp-98, Ser-116 to Gln-125, Leu-142 to Phe-151,Phe-169 to Arg-174, Ile-181 to Glu-190, Thr-243 to Gly-248.

[0359] The tissue distribution in pancreas indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection, treatment, and/or prevention of various endocrinedisorders and cancers, particularly Addison's disease, Cushing'sSyndrome, and disorders and/or cancers of the pancrease (e.g., diabetesmellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-,hypopituitarism), thyroid (e.g., hyper-, hypothyroidism), parathyroid(e.g., hyper-,hypoparathyroidism), hypothallamus, and testes.Alternatively, the expression within bone marrow indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of hematopoetic related disorders suchas anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia sincestromal cells are important in the production of cells of hematopoieticlineages. The uses include bone marrow cell ex vivo culture, bone marrowtransplantation, bone marrow reconstitution, radiotherapy orchemotherapy of neoplasia. The gene product may also be involved inlymphopoiesis, therefore, it can be used in immune disorders such asinfection, inflammation, allergy, immunodeficiency etc. In addition,this gene product may have commercial utility in the expansion of stemcells and committed progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types.

[0360] Moreover, the protein product of this gene could be used in thetreatment and/or detection of kidney diseases including renal failure,nephritus, renal tubular acidosis, proteinuria, pyuria, edema,pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome,glomerulonephritis, hematuria, renal colic and kidney stones, inaddition to Wilm's Tumor Disease, and congenital kidney abnormalitiessuch as horseshoe kidney, polycystic kidney, and Falconi's syndrome.Considering the homology to a conserved cell division control proteinindicates that the protein may show utility in the diagnosis,prevention, and/or treatment of developmental disorders, and may evenserve as a suppressor in tumorigenesis. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0361] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:59 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1565 of SEQID NO:59, b is an integer of 15 to 1579, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:59, and whereb is greater than or equal to a+14.

[0362] Features of Protein Encoded by Gene No: 50

[0363] The translation product of this gene was shown to have homologyto the chicken LRP/alpha-2-macroglobulin receptor which is thought toplay a pivitol role on the metabolism of alpha-2-macroglubulins, as wellas, complexes between plasminogen activators and their endogenousinhibitors (See Genbank Accession No.gb|X74904|GGLRPA2MR).

[0364] This gene is expressed primarily in neuronal tissues, and to alesser extent in uterine cancer.

[0365] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, neuronaldisorders and uterine cancer. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe central neuron system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., neural, reproductive, cancerous and wounded tissues)or bodily fluids (e.g., amniotic fluid, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0366] The tissue distribution in neuronal tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection/treatment of neurodegenerative disease states andbehavioural disorders such as Alzheimers Disease, Parkinsons Disease,Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia,paranoia, obsessive compulsive disorder, panic disorder, learningdisabilities, ALS, psychoses, autism, and altered behaviors, includingdisorders in feeding, sleep patterns, balance, and perception. Inaddition, the gene or gene product may also play a role in the treatmentand/or detection of developmental disorders associated with thedeveloping embryo, sexually-linked disorders, or disorders of thecardiovascular system. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0367] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:60 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1227 of SEQID NO:60, b is an integer of 15 to 1241, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:60, and whereb is greater than or equal to a+14.

[0368] Features of Protein Encoded by Gene No: 51

[0369] This gene is expressed primarily in uterine cancer.

[0370] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, uterinecancer, and other reproductive disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the uterine cancer, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., reproductive, cancerous and woundedtissues) or bodily fluids (e.g., amniotic fluid, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0371] The tissue distribution in tumors of the uterus indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and intervention of these tumors or proliferativeconditions, in addition to other tumors or cell types. Protein, as wellas, antibodies directed against the protein may show utility as atissue-specific marker and/or immunotherapy target for the above listedtissues.

[0372] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:61 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 916 of SEQID NO:61, b is an integer of 15 to 930, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:61, and where bis greater than or equal to a+14.

[0373] Features of Protein Encoded by Gene No: 52

[0374] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: VKPPDQSCNHWRDEQCLV (SEQ ID NO: 494).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0375] This gene is expressed primarily in wilm's tumor.

[0376] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, Wilm'stumor, and other urogenital disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the Wilm's tumor, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., urogenital, cancerous and woundedtissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluidand spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0377] The tissue distribution in Wilm's tumor indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis and treatment of Wilm's tumor. Protein, as well as,antibodies directed against the protein may show utility as atissue-specific marker and/or immunotherapy target for the above listedtissues. Furthermore, this gene or gene product is useful in thetreatment and/or detection of kidney diseases including renal failure,nephritus, renal tubular acidosis, proteinuria, pyuria, edema,pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome,glomerulonephritis, hematuria, renal colic and kidney stones, inaddition to congenital kidney abnormalities such as horseshoe kidney,polycystic kidney, and Falconi's syndrome. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0378] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:62 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 984 of SEQID NO:62, b is an integer of 15 to 998, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:62, and where bis greater than or equal to a+14.

[0379] Features of Protein Encoded by Gene No: 53

[0380] The translation product of this gene was shown to have homologyto the MEK kinase 3 of Mus musculus, mutations of which and/or aberrantregulation of, may provide a predisposition to cancer. The gene encodingthe disclosed cDNA is thought to reside on chromosome 17. Accordingly,polynucleotides related to this invention are useful as a marker inlinkage analysis for chromosome 17.

[0381] This gene is expressed primarily in pituitary, and to a lesserextent in ulcerative colitis and hematopoietic cells.

[0382] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune,gastrointestinal, hematopoietic diseases. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the neuronal and immune tissues, expression of this geneat significantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., neuronal, immune, cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0383] The tissue distribution in hematopoietic tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product in ulcerative colitisindicates a role in the regulation of the proliferation; survival;differentiation; and/or activation of potentially all hematopoietic celllineages, including blood stem cells. This gene product may be involvedin the regulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g., by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the natural gene product may be involved inimmune functions. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, and leukemia. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tumors and tissues. Inaddition, this gene product may have commercial utility in the expansionof stem cells and committed progenitors of various blood lineages, andin the differentiation and/or proliferation of various cell types.

[0384] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:63 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1179 of SEQID NO:63, b is an integer of 15 to 1193, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:63, and whereb is greater than or equal to a+14.

[0385] Features of Protein Encoded by Gene No: 54

[0386] When tested against Jurkat T-cell cell lines, supernatantsremoved from cells containing this gene activated the GAS (gammaactivation site) pathway. Thus, it is likely that this gene activatesT-cells through the Jaks-STAT signal transduction pathway. GAS (gammaactivation site) is a promoter element found upstream in many geneswhich are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is alarge, signal transduction pathway involved in the differentiation andproliferation of cells. Therefore, activation of the Jaks-STATs pathway,reflected by the binding of the GAS element, can be used to indicateproteins involved in the proliferation and differentiation of cells.

[0387] This gene is expressed primarily in fetal spleen and adiposetissues.

[0388] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immune,metabolic, and developmental disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the fetal spleen and adipose tissues, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., immune, developing, cancerousand wounded tissues) or bodily fluids (e.g., lymph, serum, plasma,urine, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0389] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 203 as residues: Tyr-41 to Phe-47.

[0390] The tissue distribution in fetal liver/spleen, combined with thedetection of GAS promoter activation activity, indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of a variety of immunesystem disorders. Expression of this gene product in fetal spleenindicates a role in the regulation of the proliferation; survival;differentiation; and/or activation of potentially all hematopoietic celllineages, including blood stem cells. This gene product may be involvedin the regulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g., by boosting immune responses).

[0391] Since the gene is expressed in cells of lymphoid origin, thenatural gene product may be involved in immune functions. Therefore itmay be also used as an agent for immunological disorders includingarthritis, asthma, immune deficiency diseases such as AIDS, andleukemia. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tumors and tissues. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0392] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:64 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 816 of SEQID NO:64, b is an integer of 15 to 830, where both a arid b correspondto the positions of nucleotide residues shown in SEQ ID NO:64, and whereb is greater than or equal to a+14.

[0393] Features of Protein Encoded by Gene No: 55

[0394] This gene is expressed primarily in IL-1/TNF stimulated synovialand human adipose tissues.

[0395] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,rheumatoid arthritis or obessity, and disorders of the musculo-skeletalsystem. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune and musculo-skeletal systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., synovial and adiposecells and tissues, musculo-skeletal, and cancerous and wounded tissues)or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0396] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 204 as residues: Leu-37 to Arg-45, Ser-60 to Ser-65.

[0397] The tissue distribution in synovial tissue and adipose tissueindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the diagnosis or treatment of rheumatoid arthritisor other immune diseases. In addition, the expression of this geneproduct in synovium indicates a role in the detection and treatment ofdisorders and conditions affecting the skeletal system, in particularosteoporosis as well as disorders afflicting connective tissues (e.g.arthritis, trauma, tendonitis, chrondomalacia and inflammation), such asin the diagnosis or treatment of various autoimmune disorders such asrheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well asdwarfism, spinal deformation, and specific joint abnormalities as wellas chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita,familial osteoarthritis, Atelosteogenesis type II, metaphysealchondrodysplasia type Schmid).

[0398] The tissue distribution in adipose tissue indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment of obesity and other metabolic and endocrineconditions or disorders. Furthermore, the protein product of this genemay show utility in ameliorating conditions which occur secondary toaberrant fatty-acid metabolism (e.g. aberrant myelin sheathdevelopment), either directly or indirectly. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0399] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:65 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 853 of SEQID NO:65, b is an integer of 15 to 867, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:65, and where bis greater than or equal to a+14.

[0400] Features of Protein Encoded by Gene No: 56

[0401] When tested against K562 leukemia cell lines, supernatantsremoved from cells containing this gene activated the ISRE assay. Thus,it is likely that this gene activates leukemia cells through theJak-STAT signal transduction pathway. The interferon-sensitive responseelement is a promoter element found upstream of many genes which areinvolved in the Jak-STAT pathway. The Jak-STAT pathway is a large,signal transduction pathway involved in the differentiation andproliferation of cells. Therefore, activation of the Jak-STAT pathway,reflected by the binding of the ISRE element, can be used to indicateproteins involved in the proliferation and differentiation of cells.

[0402] This gene is expressed primarily in aortic endothelium, and to alesser extent in melanocyte.

[0403] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,cardiovascular diseases. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thecardiovascular system, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g., vascular, cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0404] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 205 as residues: Met-1 to Trp-12, Arg-33 to Ser-53.

[0405] The tissue distribution in human aortic endothelial cellsindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the detection or intervention of cardiovasculardiseases, such as hypertension, cadiovascular injuries, congenital heartdiseases, ischemic heart diseases, rheumatic and other hypersensitivitydiseases, cardiomyopathy, restenosis, atherosclerosis, stoke, angina,thrombosis, and wound healing. Protein, as well as, antibodies directedagainst the protein may show utility as a tissue-specific marker and/orimmunotherapy target for the above listed tissues.

[0406] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:66 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 671 of SEQID NO:66, b is an integer of 15 to 685, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:66, and where bis greater than or equal to a+14.

[0407] Features of Protein Encoded by Gene No: 57

[0408] The translation product of this gene shares sequence homologywith prostaglandin EP3-9 receptor, which is thought to be important inprostaglandin hormonal reaction. In specific embodiments, polypeptidesof the invention comprise the following amino acid sequence:MAIPAFSSCQQISSAAALQI (SEQ ID NO: 495), and/or CNGPFKHFSFTVST (SEQ ID NO:496). Polynucleotides encoding these polypeptides are also encompassedby the invention.

[0409] This gene is expressed primarily in human retina.

[0410] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, glaucomaor other ocular diseases. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe ocular system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., retinal and other optic tissue, tissue of the nervous system, andcancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0411] The tissue distribution in retinal tissues and the homology toprostaglandin receptor indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the detection and interventionof ocular diseases like glaucoma. Specifically, the receptor can be usedfor the identification of agonists or antagonists, anti-inflammatoriesfor the eyes, and vasoconstrictive agents, etc. Furthermore, the tissuedistribution in retina indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the treatment and/or detectionof eye disorders including blindness, color blindness, impaired vision,short and long sightedness, retinitis pigmentosa, retinitis proliferans,and retinoblastoma.

[0412] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:67 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 787 of SEQID NO:67, b is an integer of 15 to 801, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:67, and where bis greater than or equal to a+14.

[0413] Features of Protein Encoded by Gene No: 58

[0414] The translation product of this gene shares weak sequencehomology with Hemophilus influenzae outmembrane protein P6 which isthought to be important in host cell interaction.

[0415] This gene is expressed primarily in human adrenal gland tumor.

[0416] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, adrenalinsufficiency or hyperfunction, adrenal gland tumors. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the endocrine systems and cancersthereof, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,adrenal gland, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0417] The tissue distribution in adrenal gland tumor and homology toHaemophilus influenzae outer membrane protein suggest thatpolynucleotides and polypeptides corresponding to this gene are usefulfor adrenal insufficiencies or hyperfunction, because a secretoryprotein from an endocrine organ may function as a hormone. The proteinproduct of this gene is also useful as a diagnostic and/or treatment foradrenal gland tumors, as well as tumors of other tissues whereexpression has been observed. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0418] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:68 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 894 of SEQID NO:68, b is an integer of 15 to 908, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:68, and where bis greater than or equal to a+14.

[0419] Features of Protein Encoded by Gene No: 59

[0420] When tested against a Jurkat T-cell line, supernatants removedfrom cells containing this gene activated the GAS (gamma activationsite) pathway. Thus, it is likely that this gene activates T-cellsthrough the Jaks-STAT signal transduction pathway. The GAS is a promoterelement found upstream in many genes which are involved in the Jaks-STATpathway. The Jaks-STAT pathway is a complex, signal transduction pathwayinvolved in the differentiation and proliferation of cells. Therefore,activation of the Jaks-STATs pathway, reflected by the binding of theGAS element, can be used to indicate proteins involved in theproliferation and differentiation of cells.

[0421] This gene is expressed primarily in human kidney pyramid, and toa lesser extent in human brain.

[0422] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,nephrotic, nephritic syndromes, renal failure, hypertensivenephrosclerosis. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of therenal system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,renal, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0423] The tissue distribution in kidney indicates that polynucleotidesand polypeptides corresponding to this gene are useful for renaldiseases, including renal failure, nephritus, renal tubular acidosis,proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephroticsyndrome, crush syndrome, glomerulonephritis, hematuria, renal colic andkidney stones, in addition to Wilm's Tumor Disease, and congenitalkidney abnormalities such as horseshoe kidney, polycystic kidney, andFalconi's syndrome. Additionally, the gene product may have endocrinefunctions related to renal function, metabolism and homeostasis.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0424] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:69 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 682 of SEQID NO:69, b is an integer of 15 to 696, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:69, and where bis greater than or equal to a+14.

[0425] Features of Protein Encoded by Gene No: 60

[0426] This gene is expressed primarily in both normal or canceroushuman breast tissue.

[0427] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,Non-neoplastic breast diseases or breast cancers. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the breast, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., mammary tissue, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0428] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 209 as residues: Pro-20 to Ser-28.

[0429] The tissue distribution in breast indicates that polynucleotidesand polypeptides corresponding to this gene are useful for eithernon-neoplastic breast diseases, such as congentital anomalities,gynecomastia, mastitis and abscess, duct ectasia and fat necrosis, orneoplasia in the breast. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0430] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:70 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 441 of SEQID NO:70, b is an integer of 15 to 455, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:70, and where bis greater than or equal to a+14.

[0431] Features of Protein Encoded by Gene No: 61

[0432] When tested against a K562 cell line, supernatants removed fromcells containing this gene activated the ISRE (interferon-sensitiveresponsive element) pathway. Thus, it is likely that this gene activatesleukemia cells, or more generally, immunr or hematopoietic cells, orother cells or cell-types, through the Jaks-STAT signal transductionpathway. The ISRE is a promoter element found upstream in many geneswhich are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is acomplex, signal transduction pathway involved in the differentiation andproliferation of cells. Therefore, activation of the Jaks-STATs pathway,reflected by the binding of the ISRE element, can be used to indicateproteins involved in the proliferation and differentiation of cells. Inspecific embodiments, polypeptides of the invention comprise thefollowing amino acid sequence: IRHERLWAELALLTGRNE (SEQ ID NO: 497).Polynucleotides encoding these polypeptides are also encompassed by theinvention. The gene encoding the disclosed cDNA is thought to reside onchromosome 3. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 3.

[0433] This gene is expressed primarily in activated T-cells andosteoarthritis, and to a lesser extent in aortic endothelium andplacenta.

[0434] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,inflammatory conditions, vascular disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune system and vascular tissues, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types and cell types (e.g., T-cellsand other cells and tissue of the immune system, bone tissue,endothelium and placenta, vascular tissue, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0435] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 210 as residues: Gln-36 to Glu-49, Glu-51 to Leu-66, Asp-68to Ser-73.

[0436] The tissue distribution in activated T-cells and underinflammatory conditions like osteoarthritis suggest that the proteinproduct of this gene is involved in the inflammatory reactions.Therefore it may be useful in the diagnosis or intervention in theinflammatory diseases with the involvement of T-cells, includingosteoarthritis. Furthermore, the tissue distribution indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis and/or treatment of disorders of the placenta.Specific expression within the placenta indicates that this gene productmay play a role in the proper establishment and maintenance of placentalfunction.

[0437] Alternately, this gene product may be produced by the placentaand then transported to the embryo, where it may play a crucial role inthe development and/or survival of the developing embryo or fetus.Expression of this gene product in a vascular-rich tissue such as theplacenta also indicates that this gene product may be produced moregenerally in endothelial cells or within the circulation. In suchinstances, it may play more generalized roles in vascular function, suchas in angiogenesis. It may also be produced in the vasculature and haveeffects on other cells within the circulation, such as hematopoieticcells. It may serve to promote the proliferation, survival, activation,and/or differentiation of hematopoietic cells, as well as other cellsthroughout the body.

[0438] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:71 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 399 of SEQID NO:71, b is an integer of 15 to 413, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:71, and where bis greater than or equal to a+14.

[0439] Features of Protein Encoded by Gene No: 62

[0440] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:GTESPMVMCCREVSQSENCLFLDTTFRFIFGKTFTNHDYISIHFYFLKAFLFSFFYSNV (SEQ ID NO:498). Polynucleotides encoding these polypeptides are also encompassedby the invention.

[0441] This gene is expressed primarily in breast lymph nodes, B-celllymphoma, and to a lesser extent in neutrophils and bone marrow cells.

[0442] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,inflammation, immunodeficiency, allergy. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., blood cells,hematopoietic cells, and cells and tissue of the immune system,cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0443] The tissue distribution in the cells of immunological functionsindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the diagnosis or intervention of immunologicallymediated disorders, such as allergy, immunodeficiency, immunesurveillance, etc. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0444] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:72 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 835 of SEQID NO:72, b is an integer of 15 to 849, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:72, and where bis greater than or equal to a+14.

[0445] Features of Protein Encoded by Gene No: 63

[0446] The translation product of this gene shares weak sequencehomology with Interferon induced 1-8 gene encoded polypeptide, which isthought to be important in retroviral REV responsive element binding andthus viral replication.

[0447] This gene is expressed primarily in B-cell lymphoma.

[0448] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immuneresponse to viral infections and other immunologically relateddisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types andcell types (e.g., T-cells and other cells and tissue of the immunesystem, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0449] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 212 as residues: Pro-47 to Asn-53. The tissue distribution inB-cell lymphoma and homology to interferon induced 1-8 gene indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the intervention of viral infection and other immunologicallyrelated disorders. The homology with interferon induced 1-8 REV responseelement binding gene indicates the gene product may bind to viralcomponents to interfere with the entry, packaging, replication, orinduce the host cell anti-viral response by intereferon mediatedpathways. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0450] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:73 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 491 of SEQID NO:73, b is an integer of 15 to 505, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:73, and where bis greater than or equal to a+14.

[0451] Features of Protein Encoded by Gene No: 64

[0452] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: IRHEEKGGKAQRWAE (SEQ ID NO: 499).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0453] This gene is expressed primarily in bone marrow.

[0454] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,hemapoiesis disorders. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thehemapoietic system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., bone marrow, and cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0455] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 213 as residues: Thr-45 to Tyr-50.

[0456] The tissue distribution in bone marrow indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor hemapoiesis disorders. The gene product may function as a growthfactor or mobilization agent for the cells of myeloid or lymphoidlineages. Furthermore, the polypeptides or polynucleotides are alsouseful to enhance or protect proliferation, differentiation, andfunctional activation of hematopoietic progenitor cells (e.g., bonemarrow cells), useful in treating cancer patients undergoingchemotherapy or patients undergoing bone marrow transplantation.Protein, as well as, antibodies directed against the protein may showutility as a tissue-specific marker and/or immunotherapy target for theabove listed tissues.

[0457] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:74 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 705 of SEQID NO:74, b is an integer of 15 to 719, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:74, and where bis greater than or equal to a+14.

[0458] Features of Protein Encoded by Gene No: 65

[0459] The translation product of this gene shares sequence homologyfamilial adenomatous polyposis gene which is thought to be important inthe tumorigenesis of colon cancer (see, e.g., Fulton, Nature 368, 32-38(1994); accession no. U28412; Joslyn et al., Cell 66 (3), 601-613(1991); accession no. M73547; and Spirio et al., Nucleic Acids Res. 19(22), 6348 (1991)). In specific embodiments, polypeptides of theinvention comprise the following amino acid sequence: CRWRPESAAPC (SEQID NO: 500), TRPGRGAQAPVK (SEQ ID NO: 501), MVSWMISRAVVLVFGMLYPAY (SEQID NO: 502), GMLYPAYYSYKAVKTKN (SEQ ID NO: 503), EYVRWMMYWIVFALYTV (SEQID NO: 504), YPAYYSYKAVKTKNVKE (SEQ ID NO: 505), VAWFPLYYELKIA (SEQ IDNO: 506), and/orMVSWMISRAVVLVFGMLYPAYYSYKAVKTKNVKEYVRWMMYWTVFALYTVIETVADQTVAWFPLYYELKIAFVIWLLSPYTKGASLIYRKFLHPLLSSKEREIDDYIVQAKERGYETMVNFGRQGLNLAATAAVTAAVKSQGAITERLRSFSMHDLTTIQGDEPVGQRPYQPLPEAKKKSXQPPVNQXVMEFHXKTXMXKQXKKQRGHIQIMRC(SEQ ID NO: 507). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0460] This gene is expressed primarily in osteoclastoma, prostate, bonemarrow and to a lesser extent in testes and dendritic cells. Northerndata has demonstrated that an abundant 1.3 kb band is seen in testestissues.

[0461] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, coloncancer and cancers of various origin, including osteoclastoma andprostate cancer, as well as reproductive disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the tumorigenesis and reproductivedisorders, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types andcell types (e.g., bone, prostate, reproductive, bone marrow, colon andother gastrointestinal tissue, tissue of the nervous system, and testisand other reproductive tissue, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0462] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 214 as residues: Ser-59 to Ile-64, Ala-71 to Tyr-76, Pro-125to Ser-141.

[0463] The tissue distribution in osteoclastoma, prostate, bone marrowand homology to familial adenomatous polyposis gene indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor diagnosis and intervention of tumors of various origins, includingcolon cancer, osteoclastoma and prostate cancer. Alternatively, theNorthern data demonstrating expression in testes tissues indicates thatthe translation product of this gene is useful for the diagnosis and/ortreatment of reproductive disorders and conditions concerning propertesticular function (e.g., endocrine function, sperm maturation), aswell as cancer. Therefore, this gene product is useful in the treatmentof male infertility and/or impotence.

[0464] This gene product is also useful in assays designed to identifybinding agents, as such agents (antagonists) are useful as malecontraceptive agents. Similarly, the protein is believed to be useful inthe treatment and/or diagnosis of testicular cancer. The testes are alsoa site of active gene expression of transcripts that may be expressed,particularly at low levels, in other tissues of the body. Therefore,this gene product may be expressed in other specific tissues or organswhere it may play related functional roles in other processes, such ashematopoiesis, inflammation, bone formation, and kidney function, toname a few possible target indications.

[0465] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:75 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence is cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1260 of SEQID NO:75, b is an integer of 15 to 1274, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:75, and wherethe b is greater than or equal to a+14.

[0466] Features of Protein Encoded by Gene No: 66

[0467] The translation product of this gene shares regional and weaksequence homology with neu differentiation factor and a serine proteaseN-terminal fragment which contains a EGF-like domain and is thought tobe important in the growth and differentiation of several cell types,including colon epithelial cells and Schwann cells.

[0468] This gene is expressed primarily in fetal lung, bone marrow,fetal liver, and to a lesser extent in brain.

[0469] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, tissueinjuries or diseases in lung, bone marrow, or liver. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the liver and lung, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types and cell types (e.g., lung andpulmonary tissue, bone marrow, hepatic tissue, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0470] The tissue distribution in fetal liver, combined with thehomology to neu differentiation factor indicates that polynucleotidesand polypeptides corresponding to this gene are useful for the diagnosisor intervention of liver or lung injuries, including hepatic failure,recovery from hepatitis, cirrhosis, hepatoblastoma, jaundice, livermetabolic diseases and conditions that are attributable to thedifferentiation of hepatocyte progenitor cells, and complications fromliver transplantation. Moreover, the protein product of this clone isuseful for the treatment and diagnosis of hematopoietic relateddisorders such as anemia, pancytopenia, leukopenia, thrombocytopenia orleukemia since stromal cells are important in the production of cells ofhematopoietic lineages The uses include bone marrow cell ex-vivoculture, bone marrow transplantation, bone marrow reconstitution,radiotherapy or chemotherapy of neoplasia. The gene product may also beinvolved in lymphopoiesis, therefore, it can be used in immune disorderssuch as infection, inflammation, allergy, immunodeficiency etc. Inaddition, this gene product may have commercial utility in the expansionof stem cells and committed progenitors of various blood lineages, andin the differentiation and/or proliferation of various cell types.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0471] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:76 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 505 of SEQID NO:76, b is an integer of 15 to 519, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:76, and where bis greater than or equal to a+14.

[0472] Features of Protein Encoded by Gene No: 67

[0473] This gene is expressed primarily in activated T-cells.

[0474] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,arthritis, asthma, auto-immune and immunodeficiency diseases. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types and cell types (e.g., T-cells and othercells and tissue of the immune system, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0475] The expression of this gene in T-cells indicates a potential rolein the treament/detection of immune disorders such as arthritis, asthma,hypersensitivity reactions and transplant rejection, and also in immunedeficiency diseases such as AIDS, and leukemia. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0476] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:77 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 375 of SEQID NO:77, b is an integer of 15 to 389, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:77, and where bis greater than or equal to a+14.

[0477] Features of Protein Encoded by Gene No: 68

[0478] The gene encoding the disclosed cDNA is thought to reside onchromosome 7. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 7.

[0479] This gene is expressed primarily in brain, and to a lesser extentin breast.

[0480] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,neurodegenerative conditions and behavioural disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the central nervous system, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., brain and other tissueof the nervous system, mammary tissue, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0481] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 217 as residues: Leu-40 to His-46.

[0482] The tissue distribution in brain indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thedetection/treatment of neurodegenerative disease states and behaviouraldisorders such as Alzheimers Disease, Parkinsons Disease, HuntingtonsDisease, schizophrenia, mania, dementia, paranoia, obsessive compulsivedisorder and panic disorder. In addition, the gene or gene product mayalso play a role in the treatment and/or detection of developmentaldisorders associated with the developing embryo, or sexually-linkeddisorders. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0483] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:78 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 809 of SEQID NO:78, b is an integer of 15 to 823, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:78, and where bis greater than or equal to a+14.

[0484] Features of Protein Encoded by Gene No: 69

[0485] The translation product of this gene shares sequence homologywith a rat secretory carrier membrane protein which is believed to playa role in cell surface re-cycling. See e.g., Brand et al., EMBO J 1993October;12(10):3753-3761. Secretory carrier membrane proteins (SCAMPs)are widely distributed as components of post-Golgi membranes thatfunction as recycling carriers to the cell surface. In fibroblasts,SCAMPs are concentrated in compartments involved in the endocytosis andrecycling of cell surface receptors while in neurons and other celltypes having regulated transport pathways, SCAMPs are also components ofregulated carriers (synaptic vesicles, secretion granules andtransporter vesicles). Their presence in multiple pathways distinguishesthem from proteins (e.g., recycling cell surface receptors and synapticvesicle proteins) which are concentrated in selected pathways. TheSCAMPs also do not appear to reside beyond the boundaries of thesepathways. This distribution indicates that SCAMPs are general markers ofmembranes that function in cell surface recycling. Accordingly,polpeptides of the invention and antibodies thereto, may be used toidentify membranes that function in cell surface recycling. The geneencoding the disclosed cDNA is thought to reside on chromosome 15.Accordingly, polynucleotides related to this invention are useful as amarker in linkage analysis for chromosome 15.

[0486] This gene is expressed primarily in hematopoietic cell types.

[0487] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immuneand hematopoetic disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune and hematopoetic systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., hematopoietic cells,and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0488] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 218 as residues: Ser-25 to Gly-31, Gln-149 to Ser-155.

[0489] The hematopoetic tissue distribution and homology to a cellsurface molecule indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the detection and/or treatmentof immune or hematopoietic disorders including arthritis, asthma andimmunodeficiency diseases. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0490] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:79 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 2441 of SEQID NO:79, b is an integer of 15 to 2455, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:79, and whereb is greater than or equal to a+14.

[0491] Features of Protein Encoded by Gene No: 70

[0492] The gene encoding the disclosed cDNA is thought to reside onchromosome 4. Accordingly, polynucleotides related to this invention areuseful as a marker in linkage analysis for chromosome 4. When testedagainst a Jurkat T-cell line, supernatants removed from cells containingthis gene activated the GAS (gamma activation site) pathway. Thus, it islikely that this gene activates T-cells through the Jaks-STAT signaltransduction pathway. The GAS is a promoter element found upstream inmany genes which are involved in the Jaks-STAT pathway. The Jaks-STATpathway is a complex, signal transduction pathway involved in thedifferentiation and proliferation of cells. Therefore, activation of theJaks-STATs pathway, reflected by the binding of the GAS element, can beused to indicate proteins involved in the proliferation anddifferentiation of cells.

[0493] This gene is expressed primarily in brain.

[0494] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,neurodegenerative conditions and behavioural disorders. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the brain and central nervous system,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g., brain andother tissues of the nervous system, and cancerous and wounded tissues)or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0495] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 219 as residues: Asp-57 to Gly-64.

[0496] The tissue distribution of this gene primarily in brain indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the treatment and/or detection of neurodegenerative diseasestates and behavioural disorders such as Alzheimers Disease, ParkinsonsDisease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia,obsessive compulsive disorder and panic disorder. In addition, the geneor gene product may also play a role in the treatment and/or detectionof developmental disorders associated with the developing embryo, orsexually-linked disorders. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0497] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:80 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 907 of SEQID NO:80, b is an integer of 15 to 921, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:80, and where bis greater than or equal to a+14.

[0498] Features of Protein Encoded by Gene No: 71

[0499] This gene is expressed primarily in hematopoietic progenitorcells (CD34+cells).

[0500] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,autoimmune and immunodeficiency disease states. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the hematopoietic system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., hematopoietic cells,and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0501] The tissue distribution of this gene predominantly inhematopoietic progenitor cell types indicates that the gene could beimportant for the treatment or detection of immune or hematopoieticdisorders including arthritis, asthma, immunodeficiency diseases,leukemia, hypersensitivity and transplant rejection. Additionally,expression of this gene product in CD34+ cells indicates a role in theregulation of the proliferation; survival; differentiation; and/oractivation of potentially all hematopoietic cell lineages, includingblood stem cells. This gene product may be involved in the regulation ofcytokine production, antigen presentation, or other processes that mayalso suggest a usefulness in the treatment of cancer (e.g., by boostingimmune responses).

[0502] Since the gene is expressed in cells of lymphoid origin, the geneor protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. In addition, this geneproduct may have commercial utility in the expansion of stem cells andcommitted progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0503] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:81 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 664 of SEQID NO:8 1, b is an integer of 15 to 678, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:81, and whereb is greater than or equal to a+14.

[0504] Features of Protein Encoded by Gene No: 72

[0505] This gene is expressed primarily in hematopoietic progenitorcells (CD34+ cells).

[0506] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,auto-immune and immunodeficiency disease states. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the hematopoietic system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., hematopoietic cells,and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0507] The tissue distribution of this gene predominantly inhematopoietic progenitor cell types indicates that the gene is importantfor the treatment or detection of immune or hematopoietic disordersincluding arthritis, asthma, immunodeficiency diseases, leukemia, andtransplant rejection. Expression of this gene product in CD34+ cellsindicates a role in the regulation of the proliferation; survival;differentiation; and/or activation of potentially all hematopoietic celllineages, including blood stem cells. This gene product may be involvedin the regulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses).

[0508] Since the gene is expressed in cells of lymphoid origin, the geneor protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. In addition, this geneproduct may have commercial utility in the expansion of stem cells andcommitted progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0509] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:82 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 843 of SEQID NO:82, b is an integer of 15 to 857, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:82, and where bis greater than or equal to a+14.

[0510] Features of Protein Encoded by Gene No: 73

[0511] The translation product of this gene shares sequence homologywith rat synaptogyrin which is thought to be important in membranetrafficking (see e.g., Stenius et al., J. Cell Biol. 131 (6 Pt 2),1801-1809 (1995)). In specific embdodiments, polypeptides of theinvention comprise the following amino acid sequences: QPYQVLPSRQVFALI(SEQ ID NO: 508), VFSCIYGEGYSNAHESKQMYCVFN (SEQ ID NO: 509),RNEDACRYGSAIGVLAFL (SEQ ID NO: 510), LVVDAYFPQISNATDRK (SEQ ID NO: 511),and/or SALWTFLWFVGFCFLTNQWAVTNPK (SEQ ID NO: 512). Polynucleotidesencoding these polypeptides are also encompassed by the invention.

[0512] This gene is expressed primarily in breast and ovary, and to alesser extent in most hematopoietic tissue types.

[0513] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, femaleinfertility and female reproductive abnormalities. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the reproductive system, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., mammary tissue, andovary and other reproductive tissue, and cancerous and wounded tissues)or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0514] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 222 as residues: Pro-9 to Trp-18, Thr-20 to Ala-27.

[0515] The tissue distribution in ovary and breast and homology to aprotein involved in membrane trafficking indicates that this protein mayplay a role in the detection/treatment of female fertility disorders,endocrine disorders, ovarian failure, amenorrhea, ovarian cancer, andalso potentially in both non-neoplastic breast diseases such ascongenital abnormalities and neoplasia in the breast. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0516] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:83 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1963 of SEQID NO:83, b is an integer of 15 to 1977, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:83, and whereb is greater than or equal to a+14.

[0517] Features of Protein Encoded by Gene No: 74

[0518] The gene encoding the disclosed cDNA is thought to reside onchromosome 12. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 12. Inspecific embodiments, polypeptides of the invention comprise thefollowing amino acid sequence:LNIDSFbYGKFESLLAKQHYKFSFLLPLAAGTERCKWWLKIEEASSDQCGCWFLVKCVPKPPSPCRQPPTQVSKIGHAPFFL(SEQ ID NO: 513). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0519] This gene is expressed primarily in brain, and to a lesser extentin placenta and spleen.

[0520] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,behavioural disorders and neurodegenerative disease states. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the brain and central nervous system,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g., brain andother tissue of the nervous system, spleen and other cells and tissue ofthe immune system, placenta, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0521] The tissue distribution in brain indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thedetection/treatment of neurodegenerative disease states and behaviouraldisorders such as Alzheimers Disease, Parkinsons Disease, HuntingtonsDisease, schizophrenia, mania, dementia, paranoia, obsessive compulsivedisorder and panic disorder. In addition, the gene or gene product mayalso play a role in the treatment and/or detection of developmentaldisorders associated with the developing embryo, or sexually-linkeddisorders. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0522] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:84 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1135 of SEQID NO:84, b is an integer of 15 to 1149, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:84, and whereb is greater than or equal to a+14.

[0523] Features of Protein Encoded by Gene No: 75

[0524] When tested against a K562 cell line, supernatants removed fromcells containing this gene activated the ISRE (interferon-sensitiveresponsive element) pathway. Thus, it is likely that this gene activatesleukemia cells, or more generally, in immune or hematopoietic cells, orother cells or cell-types, through the Jaks-STAT signal transductionpathway. The ISRE is a promoter element found upstream in many geneswhich are involved in the Jaks-STAT pathway. The Jaks-STAT pathway is acomplex, signal transduction pathway involved in the differentiation andproliferation of cells. Therefore, activation of the Jaks-STATs pathway,reflected by the binding of the GAS element, can be used to indicateproteins involved in the proliferation and differentiation of cells.

[0525] This gene is expressed primarily in bone marrow and spleen.

[0526] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,autoimmune diseases, transplant rejection and immundeficiency diseasestates. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thehematopoietic and immune systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0527] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 224 as residues: Pro-22 to His-33, Ser-42 to Trp-48.

[0528] The tissue distribution of this gene predominantly inhematopoietic cell types indicates that the gene is important for thetreatment or detection of immune or hematopoietic disorders includingarthritis, asthma, immunodeficiency diseases, leukemia, and transplantrejection. Furthermore, the polypeptides or polynucleotides are alsouseful to enhance or protect the proliferation, differentiation, andfunctional activation of hematopoietic progenitor cells (e.g., bonemarrow cells), useful in treating cancer patients undergoingchemotherapy or patients undergoing bone marrow transplantation. Thepolypeptides or polynucleotides are also useful to increase theproliferation of peripheral blood leukocytes, which can be used in thecombat of a range of hematopoietic disorders, includingimmmunodeficiency diseases, leukemia, and septicemia.

[0529] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:85 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence. would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 753 of SEQID NO:85, b is an integer of 15 to 767, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:85, and where bis greater than or equal to a+14.

[0530] Features of Protein Encoded by Gene No: 76

[0531] In specific embodiments, polypeptides of the invention comprisethe sequence: SLQYRIRIPGRPT (SEQ ID NO: 514), DLVTYTSSLQYRIRIPGRPTRP(SEQ ID NO: 515), VKTAECYSIPLGSCPVNIQRVR (SEQ ID NO: 517), and/orLGNKKYINIRCLEMQVTLKILCEIEKKERRGTHCLV (SEQ ID NO: 516). Polynucleotidesencoding these polypeptides are also encompassed by the invention.Contact of cells with supernatant expressing the product of this geneincreases the permeability of U937 monocyte cells to calcium. Thus, itis likely that the product of this gene is involved in a signaltransduction pathway that is initiated when the product of this genebinds a receptor on the surface of the monocyte cell. Thus,polynucleotides and polypeptides have uses which include, but are notlimited to, activating monocyte cells.

[0532] This gene is expressed in primary dendritic cells.

[0533] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,auto-immune disorders such as asthma and arthritis, in transplantrejection, leukemia and immunodeficiency disease states. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune system, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types and cell types (e.g., primary dendriticcells and other cells and tissue of the immune system, and cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0534] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 225 as residues: Gly-2 to Glu-7, Arg-27 to Gly-34.

[0535] The tissue distribution of this gene predominantly inhematopoietic cell types indicates that the gene is important for thetreatment or detection of immune or hematopoietic disorders includingarthritis, asthma, immunodeficiency diseases, leukemia, hypersensitivityand graft rejection. Expression of this gene product in primarydendritic cells also strongly indicates a role for this protein inimmune function and immune surveillance. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0536] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:86 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 714 of SEQID NO:86, b is an integer of 15 to 728, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:86, and where bis greater than or equal to a+14.

[0537] Features of Protein Encoded by Gene No: 77

[0538] This gene is expressed primarily in 12 week old early stagehuman.

[0539] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,developmental abnormalities. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe developmental system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., developing and differentiating tissue, and cancerousand wounded tissues) or bodily fluids (e.g., lymph, serum, plasma,urine, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0540] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 226 as residues: Thr-14 to Thr-19.

[0541] The expression of this gene primarily in the embryo indicates akey role in embryonic development, and could be used in the treatmentand or detection of developmental disorders. Expression within embryonictissue and other cellular sources marked by proliferating cellsindicates that this protein may play a role in the regulation ofcellular division, and may show utility in the diagnosis and treatmentof cancer and other proliferative disorders. Sinilarly, embryonicdevelopment also involves decisions involving cell differentiationand/or apoptosis in pattern formation. Thus this protein may also beinvolved in apoptosis or tissue differentiation and could again beuseful in cancer therapy. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0542] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:87 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 721 of SEQID NO:87, b is an integer of 15 to 735, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:87, and where bis greater than or equal to a+14.

[0543] Features of Protein Encoded by Gene No: 78

[0544] This gene is expressed primarily in T-cells, and to a lesserextent in cord blood and osteosarcoma.

[0545] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,auto-immune diseases, immunodeficiency diseases and host-graftrejection. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,cells and tissues of the immune system, bone, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0546] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 227 as residues: Pro-36 to Ala-41.

[0547] The expression of this gene in T-cells indicates a potential rolein the treament/detection of immune disorders such as arthritis, asthma,immune deficiency diseases such as AIDS, leukemia and transplantrejection. Expression of this gene product in T cells also stronglyindicates a role for this protein in immune function and immunesurveillance. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0548] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:88 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 875 of SEQID NO:88, b is an integer of 15 to 889, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:88, and where bis greater than or equal to a+14.

[0549] Features of Protein Encoded by Gene No: 79

[0550] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:LFYLLTCSCAPGHLAFVCSQCLPFDMGKELWPKSPSSCTSTSVAQGWGGRGRPSPYICVV (SEQ ID NO:518), IQGSRLPPLPAPLHPLPLIYLLLGSPAQSWLLVPSWGHPSTLTLTMAAEHQAWPSGFHGDH (SEQID NO: 519). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0551] This gene is expressed primarily in placenta and 9 week oldembryo, and to a lesser extent in fetal spleen.

[0552] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,developmental disorders. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thedevelopmental system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., developing and differentiating tissues, and spleen and othercells and tissue of the immune system, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0553] The expression of this gene primarily in the embryo indicates akey role in embryonic development, and could be used in the treatmentand or detection of developmental disorders. The tissue distribution inplacenta also indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the diagnosis and/or treatmentof disorders of the placenta. Specific expression within the placentaindicates that this gene product may play a role in the properestablishment and maintenance of placental function. Alternately, thisgene product may be produced by the placenta and then transported to theembryo, where it may play a crucial role in the development and/orsurvival of the developing embryo or fetus. Expression within embryonictissue and other cellular sources marked by proliferating cellsindicates that this protein may play a role in the regulation ofcellular division. Similarly, embryonic development also involvesdecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0554] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:89 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 555 of SEQID NO:89, b is an integer of 15 to 569, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:89, and where bis greater than or equal to a+14.

[0555] Features of Protein Encoded by Gene No: 80

[0556] This gene is expressed primarily in early stage brain.

[0557] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,developmental and neurodegenerative diseases of the brain and nervoussystem. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thebrain, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g., brainand other tissue of the nervous system, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0558] The tissue distribution in brain indicates that polynucleotidesand polypeptides corresponding to this gene are useful for the treatmentand detection of developmental and neurodegenerative diseases, as wellas behavioral or nervous system disorders. Examples of such conditionswould include: depression, schizophrenia, mania, dementia, paranoia,addictive behavior and sleep disorders. In addition a brain-specificgene product may be useful in the diagnosis of specific brain tumors.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0559] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:90 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 320 of SEQID NO:90, b is an integer of 15 to 334, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:90, and where bis greater than or equal to a+14.

[0560] Features of Protein Encoded by Gene No: 81

[0561] This gene is expressed primarily in synovial tissue.

[0562] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,arthritis, tendonitis and chrondomalacia. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the synovium, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., synovial tissue, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0563] The tissue distribution in synovial tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of connective tissue disorders such asarthritis, tendonitis, chrondomalacia, inflammation and trauma. Inaddition, the expression of this gene product in synovium indicates arole in the detection and treatment of disorders and conditionsaffecting the skeletal system, in particular osteoporosis as well asdisorders afflicting connective tissues (e.g. arthritis, trauma,tendonitis, chrondomalacia and inflammation), such as in the diagnosisor treatment of various autoimmune disorders such as rheumatoidarthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism,spinal deformation, and specific joint abnormalities as well aschondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familialosteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasiatype Schmid). Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0564] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:91 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 781 of SEQID NO:91, b is an integer of 15 to 795, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:91, and where bis greater than or equal to a+14.

[0565] Features of Protein Encoded by Gene No: 82

[0566] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: VDPPGCRNSARGCTRLLRGSSKI (SEQ ID NO:520). Polynucleotides encoding these polypeptides are also encompassedby the invention.

[0567] This gene is expressed primarily in the frontal cortex of thebrain.

[0568] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,developmental and neurodegenerative diseases of the brain . Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the central nervous system, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., brain and other tissueof the nervous system, and cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0569] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 231 as residues: Ser-4 to Tyr-13.

[0570] The tissue distribution in brain indicates that polynucleotidesand polypeptides corresponding to this gene are useful for the detectionand treatment of developmental and neurodegenerative diseases of thebrain and nervous system, including malignancies as well as behavioraldisorders. Examples of such conditions might include: depression,schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington'sdisease, mania, dementia, paranoia, addictive behavior and sleepdisorders. Furthermore, elevated expression of this gene product withinthe frontal cortex of the brain indicates that it may be involved inneuronal survival; synapse formation; conductance; neuraldifferentiation, etc. Such involvement may impact many processes, suchas learning and cognition. It may also be useful in the treatment ofsuch neurodegenerative disorders as schizophrenia; ALS; or Alzheimer's.

[0571] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:92 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 563 of SEQID NO:92, b is an integer of 15 to 577, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:92, and where bis greater than or equal to a+14.

[0572] Features of Protein Encoded by Gene No: 83

[0573] The translation product of this gene shares sequence homologywith the L6 cell surface antigen, which is highly expressed in lung,breast, colon, and ovarian carcinomas. See e.g., Marken et al., ProcNatl Acad Sci USA 1992 Apr 15;89(8):3503-3507. In specific embodiments,polypeptides of the invention comprise the sequence: ITLCLVCIVANA (SEQID NO: 521). Polynucleotides encoding these polypeptides are alsoencompassed by the invention. This gene was recently cloned andsequenced by another group, which identified the gene as a putativetetraspan transmembrane (TM4) protein L6H from humans. The transmembrane4 superfamily (TM4SF) or tetraspan superfamily has at least 16 members(including CD9, CD20, CD37, CD53, CD63, CD81, CD82, Al5, CO-029, Sm23,RDS, Uro B, Uro A, SAS, Rom-1, PETA3, and YKK8), is the second biggestsubfamily among CD antigen superfamilies, and are activation antigens ofT- cells. All TM4SF members contain four putative transmembrane domains,two extracellular loops, and two short cytoplasmic tails. They arevariously expressed on immature, early, mature, activated lymphocytes,monocytes, macrophages, granulocytes, platelets, eosinophils, basophils,certain leukemic and lymphoma cells, and a variety of other cells andtissues.

[0574] This gene is expressed primarily in fetal liver/spleen tissues.

[0575] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, cancersof the liver, immune system disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the hepatic and immune system, expression of this geneat significantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., lung and pulmonary tissue, colonand other gastrointestinal tissue, mammary tissue, ovarian tissue andother tissue of the reproductive system, hepatic tissue, immune systemtissues, and cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0576] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 232 as residues: Asn-32 to Asn-41, Thr-140 to Ala-147,Asp-188 to His-197.

[0577] The murine monoclonal antibody (mAb) L6 recognizes an integralmembrane glycoprotein that is highly expressed in lung, breast, colon,and ovarian carcinomas and is referred to as the L6 antigen. Thisantigen is an attractive target for therapeutic intervention due to itshigh level expression on malignant cells. The tissue distribution andhomology to L6 antigen indicates that polynucleotides and polypeptidescorresponding to this gene are useful for detection and treatment ofneoplastic tissues—particularly of the liver. The translation product ofthis gene is a member of the tetraspan transmembrane superfamily andtherefore, antigenic regions of members of this family could be valuableimmunogens or targets to implement active and passive immunotherapy inpatients with cancer. Moreover, the protein product of this clone isuseful for the treatment and diagnosis of hematopoietic relateddisorders such as anemia, pancytopenia, leukopenia, thrombocytopenia orleukemia since stromal cells are important in the production of cells ofhematopoietic lineages. The uses include bone marrow cell ex-vivoculture, bone marrow transplantation, bone marrow reconstitution,radiotherapy or chemotherapy of neoplasia. The gene product may also beinvolved in lymphopoiesis, therefore, it can be used in immune disorderssuch as infection, inflammation, allergy, immunodeficiency etc. Inaddition, this gene product may have commercial utility in the expansionof stem cells and committed progenitors of various blood lineages, andin the differentiation and/or proliferation of various cell types.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0578] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:93 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 954 of SEQID NO:93, b is an integer of 15 to 968, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:93, and where bis greater than or equal to a+14.

[0579] Features of Protein Encoded by Gene No: 84

[0580] This gene is expressed primarily in glioblastoma.

[0581] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,glioblastoma. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thecentral nervous system, expression of this gene at significantly higheror lower levels may be routinely detected in certain tissues or celltypes (e.g., tissue of the nervous system, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0582] The tissue distribution in glioblastoma indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection and treatment of malignancies, as well asdevelopmental and neurodegenerative diseases of the brain and nervoussystem. Protein, as well as, antibodies directed against the protein mayshow utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0583] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:94 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 539 of SEQID NO:94, b is an integer of 15 to 553, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:94, and where bis greater than or equal to a+14.

[0584] Features of Protein Encoded by Gene No: 85

[0585] The translation product of this gene shares sequence homologywith Tbx, which is thought to be important in developmental regulation(see e.g., Knezevic et al., Development 124, 411-419 (1997); andaccession U80951). In specific embodiments, polypeptides of theinvention comprise the sequence: VTAYQNQQITRLKIDRNPFAKGFR (SEQ ID NO:522), GTATVTAYQNQQITRL (SEQ ID NO: 523), KIDRNPFAKGFRDSGRNRMGLEAL (SEQID NO: 524), STLLQVLGMAFLPLTLTFCLA (SEQ ID NO: 525), and/orVESYAFWRPSLRT LTFEDIPGIPKQGNASS (SEQ ID NO: 526). Polynucleotidesencoding these polypeptides are also encompassed by the invention.

[0586] This gene is expressed primarily in synovial sarcoma and to alesser extent in osteoclastoma, osteoblastoma, and hemangiopericytoma.

[0587] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,osteosarcoma, osteoclastoma, and chondrosarcoma, and diseases of theskeletal system, such as osteoporosis. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the skeletal system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., bone cells andtissue, synovial cells and tissue, cartilage, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0588] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 234 as residues: Ala-45 to Asp-50, Arg-57 to Pro-63.

[0589] The tissue distribution in skeletal tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of osteoperosis, fracture, osteosarcoma,osteoclastoma, chondrosarcoma, ossification and osteonecrosis,arthritis, tendonitis, chrondomalacia, and inflammation. Elevated levelsof expression of this gene product in osteoclastoma and osteoblastomaindicates that it may play a role in the survival, proliferation, and/orgrowth of these cells. Therefore, it may be useful in influencing bonemass in such conditions as osteoporosis. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0590] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:95 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 954 of SEQID NO:95, b is an integer of 15 to 968, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:95, and where bis greater than or equal to a+14.

[0591] Features of Protein Encoded by Gene No: 86

[0592] The gene encoding the disclosed cDNA is thought to reside onchromosome 19. Accordingly, polynucleotides related to this inventionare useful as a marker in linkage analysis for chromosome 19. Thetranslation product of this gene is a transmembrane protein that formsdisulfide-bonded homodimers and contains a motif in its cytoplasmicdomain (located at the carboxy terminus of the protein relative to thetransmembrane domain) that functions as an adaptor for associatingprotein complexes involved in triggering cellular activation. Thetransmembrane domain is predicted to consist of the amino acid sequence:VLAGIVMGDLVLTVLIALAVYFLG (SEQ ID NO: 528). In specific embodiments,polypeptides of the invention comprise the following amino acidsequences: QAQSDCSCSTVSPG (SEQ ID NO: 527), VLAGIVMGDLVLTVLIALAVYFLG(SEQ ID NO: 528), VPRGRGAAEATRKQRITETESPYQELQGQRSDVYSDL (SEQ ID NO:529), and/or ETESPYQELQGQRSDVYSDLNT (SEQ ID NO: 530). Polynucleotidesencoding these polypeptides are also encompassed by the invention.

[0593] This gene is expressed primarily in macrophage, and to a lesserextent in primary dendritic cells and neutrophils.

[0594] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,immunologically mediated disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., blood cells, andcells and tissue of the immune system, and cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0595] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 235 as residues: Ala-28 to Ser-33, Ala-76 to Lys-111.

[0596] The tissue distribution in immune tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis, treatment, and/or prevention of immune disordersincluding: leukemias, lymphomas, auto-immnunities, immunodeficiencies(e.g., AIDS), immuno-supressive conditions (transplantation) andhematopoietic disorders. Furthermore, expression of this gene product inmacrophage and primary dendritic cells also strongly indicates a rolefor this protein in immune function and immune surveillance. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0597] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:96 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 683 of SEQID NO:96, b is an integer of 15 to 697, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:96, and where bis greater than or equal to a+14.

[0598] Features of Protein Encoded by Gene No: 87

[0599] This gene is expressed primarily in prostate cancer.

[0600] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, prostatecancer. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theprostate, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,prostate, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder. the tissue distribution in prostate cancerous tissue indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the detection and treatment of prostate cancer and otherprostate disorders, as well as cancers in other tissues where expressionhas been indicated. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0601] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:97 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 852 of SEQID NO:97, b is an integer of 15 to 866, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:97, and where bis greater than or equal to a+14.

[0602] Features of Protein Encoded by Gene No: 88

[0603] The translation product of this gene shares sequence homologywith retinal epithelial membrane protein (REMP), which is thought to beimportant in development and maintenance of normal retinal function (Seee.g., Philp et al., Exp. Cell Res. 219 (1), 64-73 (1995); and GenbankAccesion No.U15685). The translation product of this gene also shareshomology with monocarboxylate transporter protein (Genbank Accesionno.U87627). Another group recently cloned and sequenced this gene,describing it as a monocarboxylate transporter protein (GenbankAccession No. gi|2463634). In quantitative terms, lactic acid is one ofthe most important metabolites in the body, substantial amounts beingused and/or produced by almost all mammalian cells. As such it must berapidly transported into and out of cells. Lactic acid transport acrossthe plasma membrane is catalysed by proton-linked monocarboxylatetransporters (MCTs), which are also responsible for the transport ofpyruvate and the ketone bodies acetoacetate, -hydroxybutyrate andacetate. In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: FLCALSPLGQLLQDRYGWRGGFLILGGL (SEQ IDNO: 531), LLNCCVCAALMRPLVVTAQPGXGPPRP (SEQ ID NO: 532), and/orSRRLXDLSVFRDRGFVLYAVAASVM (SEQ ID NO: 533). Polynucleotides encodingthese polypeptides are also encompassed by the invention. The geneencoding the disclosed cDNA is thought to reside on chromosome 17.Accordingly, polynucleotides related to this invention are useful as amarker in linkage analysis for chromosome 17.

[0604] This gene is expressed primarily in neutrophils, and to a lesserextent in a variety of other tissues and cell types, including retina.

[0605] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, eye, andmetabolic and cellular transport disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the eye and immune system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types and cell types (e.g., retinal cells,neutrophils and other blood cells, and cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0606] The tissue distribution in retinal tissue and the homology toREMP indicates that polynucleotides and polypeptides corresponding tothis gene are useful for the diagnosis, treatment, and/or prevention ofeye disorders, including neoplasms, visual impairments and blindness.Alternatively, the homology to monocarboxylate transporter proteinindicates that the translation product of this gene is useful for thediagnosis and/or treatment of disorders involving the cellular transportof lactic acid into and out of the cell.

[0607] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:98 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1354 of SEQID NO:98, b is an integer of 15 to 1368, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:98, and whereb is greater than or equal to a+14.

[0608] Features of Protein Encoded by Gene No: 89

[0609] The translation product of this gene shares sequence homologywith human squamous cell E48 antigen which is thought to be important inself-recognition and immune function. In specific embodiments,polypeptides of the invention comprise the following amino acidsequences: MMATPSTRPPPPAASTTSATAPALPPRPPWPWPPSSWPPSGVSSKAPEADPLKNKAL(SEQ ID NO: 534);LLLTSPLPRCPPACSHDAPAHPDPGGPHGLTSGPGLGLPRVCLQRRQLLQPHALPGYGCLLHDHAHLLHPHQDEGQ(SEQ ID NO: 535); and/orWLLQARVHHLLLPVRPLQRHRPCHPGHPGPGPHPPGHPLGSPLKPPRQTHSRTKLS (SEQ ID NO:536). Polynucleotides encoding these polypeptides are also encompassedby the invention. When tested against K562 leukemia cell lines,supernatants removed from cells containing this gene activated the ISREassay. Thus, it is likely that this gene activates leukemia cellsthrough the Jak-STAT signal transduction pathway. Theinterferon-sensitive response element is a promoter element foundupstream of many genes which are involved in the Jak-STAT pathway. TheJak-STAT pathway is a large, signal transduction pathway involved in thedifferentiation and proliferation of cells. Therefore, activation of theJak-STAT pathway, reflected by the binding of the ISRE element, can beused to indicate proteins involved in the proliferation anddifferentiation of cells.

[0610] This gene is expressed primarily in adult brain, and to a lesserextent in fetal lung.

[0611] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,autoimmune disorders. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0612] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 238 as residues: Tyr-28 to Phe-34, Thr-54 to Val-60, Tyr-73to Thr-82.

[0613] The tissue distribution and homology to human squamous cell E48antigen indicates that polynucleotides and polypeptides corresponding tothis gene are useful for study, diagnosis and treatment of autoimmunediseases and disorders, such as lupus, transplant rejection, allergicreactions, and arthritis. Protein, as well as, antibodies directedagainst the protein may show utility as a tissue-specific marker and/orimmunotherapy target for the above listed tissues.

[0614] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:99 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 599 of SEQID NO:99, b is an integer of 15 to 613, where both a and b correspond tothe positions of nucleotide residues shown in SEQ ID NO:99, and where bis greater than or equal to a+14.

[0615] Features of Protein Encoded by Gene No: 90

[0616] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:QEFQTGLGNMVKPCLYEKYRNISWLWWHTPVVPATWEAEVGGSLEPGRLRLQ (SEQ ID NO: 537),and/or ILGGESILILSWVFSYIFFRIALEITIYILNVSPFCLGRWLMPVIPALWEAEVGGLPELRSSRPA(SEQ ID NO: 538). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0617] This gene is expressed primarily in human adult lymph nodetissue.

[0618] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immunedisorders and lymphomas. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune and metabolic systems, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., immune, metabolic, cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0619] The tissue distribution in lymph nodes indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study, diagnosis and treatment of immune and lymph diseases anddisorders such as lymphomas. This gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the natural gene product may be involved inimmune functions. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immunodeficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, granulomatousdisease, inflammatory bowel disease, sepsis, acne, neutropenia,neutrophilia, psoriasis, hypersensitivities, such as T-cell mediatedcytotoxicity; immune reactions to transplanted organs and tissues, suchas host-versus-graft and graft-versus-host diseases, or autoimmunitydisorders, such as autoimmune infertility, lense tissue injury,demyelination, systemic lupus erythematosis, drug induced hemolyticanemia, rheumatoid arthritis, Sjogren's disease, scleroderma andtissues. In addition, this gene product may have commercial utility inthe expansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0620] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:100 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 671 of SEQID NO:100, b is an integer of 15 to 685, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:100, andwhere b is greater than or equal to a+14.

[0621] Features of Protein Encoded by Gene No: 91

[0622] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: MPKQLAQLLYRLPRG (SEQ ID NO: 539),LFQAISVSGSHRQGSRTWNTLTEGNAEAACTVALQTSKRLILASRW (SEQ ID NO: 540),TLSFMNSHCVPIKALFFLSVVSYIFIMPHHIFFTVKILKSCFQVGQLMKL (SEQ ID NO: 541),and/orRPTRPITFSSNISEWVPSTGFQDLEHFNRRKCRSSLHSCFTDFQEADSGFKMEPWSWFFFFFFFFPQRTCGCALCVLFLFSIWGPHGKELLNSFLYELPLCSYKGPFLS(SEQ ID NO: 542). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0623] This gene is expressed primarily in placenta and synovium.

[0624] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases of the synovium and placenta. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the placenta and synovium, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., placenta, synovium, cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0625] The tissue distribution in placenta and synovium indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study, diagnosis and treatment of growth and developmentaldisorders and arthritic and inflammatory conditions. Expression withinembryonic tissue and other cellular sources marked by proliferatingcells indicates that this protein may play a role in the regulation ofcellular division, and may show utility in the diagnosis and treatmentof cancer and other proliferative disorders. Similarly, embryonicdevelopment also involves decisions involving cell differentiationand/or apoptosis in pattern formation. Thus this protein may also beinvolved in apoptosis or tissue differentiation and could again beuseful in cancer therapy. Specific expression within the placentaindicates that this gene product may play a role in the properestablishment and maintenance of placental function. Alternately, thisgene product may be produced by the placenta and then transported to theembryo, where it may play a crucial role in the development and/orsurvival of the developing embryo or fetus. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0626] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:101 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 632 of SEQID NO:101, b is an integer of 15 to 646, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:101, andwhere b is greater than or equal to a+14.

[0627] Features of Protein Encoded by Gene No: 92

[0628] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:VDPRVRLPLFWWQPSCAVYLFPRVYNNMCTRVLGTLPHCWDLATLLQPSSRIWGNVSEAPGM (SEQ IDNO: 543),VPYHIAGTLPHCCSLPVGYGGMSVRLQGCRYVGNVGPQGNMQSGRSWALKMVLLCNSCLGLGVGSVGPSMSSLFGAVLSETPGSSVY(SEQ ID NO: 544), and/or MLDPRATCNLVGVGLSKWCCCVTAAWVLG (SEQ ID NO: 545).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0629] This gene is expressed primarily in chronic lymphocytic leukemia.

[0630] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases of immune system including cancer. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0631] The tissue distribution in chronic lymphocytic leukemia indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the study, diagnosis and treatment of disorders of the immunesystem including cancers. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0632] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:102 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 812 of SEQID NO:102, b is an integer of 15 to 826, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:102, andwhere b is greater than or equal to a+14.

[0633] Features of Protein Encoded by Gene No: 93

[0634] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:HGDWIYVHIVEQLNQANNKSVTSHTYFVVKTCKIHSLSNFQASNTLLXTVVTMLYNRSLELILPV (SEQID NO: 546),TYSSCLTKILYSLINIYPIPHCSPAXITTILLSASMNLTFFFFRFHICEIAQYLSFCAWLISLNIKSL(SEQ ID NO: 547), and/or MNLTFFFFRFHICEIAQYLSFCAWLISLNIKSL (SEQ ID NO:548). Polynucleotides encoding these polypeptides are also encompassedby the invention.

[0635] This gene is expressed primarily in brain medulloblastoma.

[0636] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of cancerand disorders of the CNS. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe central nervous system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., brain, cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0637] The tissue distribution in brain indicates that polynucleotidesand polypeptides corresponding to this gene are useful for thediagnosis, treatment, and/or prevention of cancers and other disordersand diseases of the CNS. The tissue distribution further indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection/treatment of neurodegenerative disease states andbehavioural disorders such as Alzheimers Disease, Parkinsons Disease,Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia,paranoia, obsessive compulsive disorder, panic disorder, learningdisabilities, ALS, psychoses, autism, and altered bahaviors, includingdisorders in feeding, sleep patterns, balance, and perception. Inaddition, the gene or gene product may also play a role in the treatmentand/or detection of developmental disorders associated with thedeveloping embryo, or sexually-linked disorders. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0638] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:103 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 572 of SEQID NO:103, b is an integer of 15 to 586, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:103, andwhere b is greater than or equal to a+14.

[0639] Features of Protein Encoded by Gene No: 94

[0640] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:LVCYCSTKKEKKLHEIAIQQGQNWRWLLFYKEISVPGFQSVWCSYKCLCVVWKAGEGG (SEQ ID NO:549), RRSCSGPPLVNTAGKILSSSPAKLACKRTDFHIPSI (SEQ ID NO: 550),RASILGIDNERGCHFRHFNPLKEYKRKKKENKSFRIV (SEQ ID NO: 551),SKNKTRGGDWCVTVLRKRRKSFMKSPFSKDRTGDGFSFTKKSLSQAFSLFGVHTSVCVLCGRRGKAGEGGPVQGPLW(SEQ ID NO: 552), and/orMKSPFSKDRTGDGFSFTKKSLSQAFSLFGVHTSVCVLCGRRGKAGEGGPVQGPLW (SEQ ID NO:553). Polynucleotides encoding these polypeptides are also encompassedby the invention.

[0641] This gene is expressed primarily in meningima and neutrophils andto a lesser extent in anergic T cells and CD34 depleted buffy coat.

[0642] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,inflammatory, immune and hemopoietic disorders. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the hemopoietic, immune and inflammatory systems,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g., immune,cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0643] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 243 as residues: Glu-45 to Asn-50.

[0644] The tissue distribution in immune tissues indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study, diagnosis and treatment of various disorders and diseasesof the immune, inflammatory, and hemopoietic systems. Furthermore, thetissue distribution indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the diagnosis and/or treatmentof hematopoietic disorders. This gene product is primarily expressed inhematopoietic cells and tissues, suggesting that it plays a role in thesurvival, proliferation, and/or differentiation of hematopoieiticlineages. Expression of this gene product in T cells and neutrophilsalso strongly indicates a role for this protein in immune function andimmune surveillance. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0645] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO: 104 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 614 of SEQID NO: 104, b is an integer of 15 to 628, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO: 104, andwhere b is greater than or equal to a+14.

[0646] Features of Protein Encoded by Gene No: 95

[0647] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: MGESECYRRLSGASCTWTVHVDFA (SEQ ID NO:554); MHCGTRVWKTMKHDYFLLACLSMTSTGGILCTL 9SEQ ID NO: 555);STLSLIPTSSSLSFWPWCTAIIGSIFTYCVCVCVCFVVNLNRTCYLPNSIIYHNSKLATIIDKSMTLS(SEQ ID NO: 556); and/or MWILPKVSLICIVELGYGKP (SEQ ID NO: 557).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0648] This gene is expressed primarily in human meningima.

[0649] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,meningitis and other inflammatory conditions. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the cerebrospinal membranes, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., cancerous and wounded tissues) orbodily fluids (e.g., lymph. serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0650] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 244 as residues: Ser-35 to Phe-41.

[0651] The tissue distribution indicates that polynucleotides andpolypeptides corresponding to this gene are useful for study, treatment,and diagnosis of disorders of the meningima. The protein is also usefulin the development of inhibitors of infections, particularly, though notlimited to, the meninges or other neural-associated or neural tissue. Inaddition, the protein is useful for the treatment of injuries to themeninges, potentially in regeneration, or in congenital disorders, birthdefects, etc. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0652] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:105 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 544 of SEQID NO:105, b is an integer of 15 to 558, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:105, andwhere b is greater than or equal to a+14.

[0653] Features of Protein Encoded by Gene No: 96

[0654] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:MSTGDGRDAEKGWPVSEEENQRSVYPGYPECDERQAVPQHCAIASPSSLQSHHPASACVPRR (SEQ IDNO: 558), QQMTLGTKIKWGQLQRGQEIPTGDFTVRNFMRFSIIYC (SEQ ID NO: 559),and/or PFLFCASRIRXQGIGIHGQVACSAVRMYNNR (SEQ ID NO: 560). Polynucleotidesencoding these polypeptides are also encompassed by the invention. Thegene encoding the disclosed cDNA is thought to reside on chromosome 10.Accordingly, polynucleotides related to this invention are useful as amarker in linkage analysis for chromosome 10.

[0655] This gene is expressed primarily in neutrophils and activatedmonocytes.

[0656] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immuneand hematopoietic disorders. Similarly, polypeptides and antibodiesdirected to these polypeptides are useful in providing immunologicalprobes for differential identification of the tissue(s) or cell type(s).For a number of disorders of the above tissues or cells, particularly ofthe immune and hematopoietic systems, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0657] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 245 as residues: Met-l to Ser-6, Pro-29 to Ser-34.

[0658] The tissue distribution in monocytes and neutrophils indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the study, diagnosis and treatment of diseases of the immuneand hematopoietic systems. Expression of this gene product in monocytesand neutrophils also strongly indicates a role for this protein inimmune function and immune surveillance. This gene product may beinvolved in the regulation of cytokine production, antigen presentation,or other processes that may also suggest a usefulness in the treatmentof cancer (e.g. by boosting immune responses). Since the gene isexpressed in cells of lymphoid origin, the gene or protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0659] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:106 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 742 of SEQID NO:106, b is an integer of 15 to 756, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:106, andwhere b is greater than or equal to a+14.

[0660] Features of Protein Encoded by Gene No: 97

[0661] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:VLCEEAGQKVPSTPSWSSWTLQKRLRGSPAEANCSPSFPAPPGKE (SEQ ID NO: 561),MSLSALACDFTPIQPWEWEEYEQITLGLTAPSNLLESNYLGQASECFVRKLVRRFPQLLPGPPGHCRKDLGDPQQRPIALLPSLPHQERNNVHRLEADSEVDL(SEQ ID NO: 562), CVDFDEYFSSWEPLLKMMFKGVVGGKMKAWRRKKRRKPLPYKIHAD (SEQ IDNO: 563), and/or MMFKGVVGGKMKAWRRKKRRKPLPYKIHAD (SEQ ID NO: 564).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0662] This gene is expressed primarily in bone marrow, and to a lesserextent in testes.

[0663] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,hematopoietic and reproductive disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the hematopoietic and reproductive systems, expressionof this gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., reproductive, immune,cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0664] The tissue distribution in bone marrow and testes indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study, diagnosis and treatment of various disorders involvingthe hematopoietic and reproductive systems. The uses include bone marrowcell ex vivo culture, bone marrow transplantation, bone marrowreconstitution, radiotherapy or chemotherapy of neoplasia. The geneproduct may also be involved in lymphopoiesis, therefore, it can be usedin immune disorders such as infection, inflammation, allergy,immunodeficiency etc. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Furthermore, polynucleotides and polypeptidescorresponding to this gene are useful for the treatment and diagnosis ofconditions concerning proper testicular function (e.g. endocrinefunction, sperm maturation), as well as cancer. Therefore, this geneproduct is useful in the treatment of male infertility and/or impotence.This gene product is also useful in assays designed to identify bindingagents, as such agents (antagonists) are useful as male contraceptiveagents.

[0665] Similarly, the protein is believed to be useful in the treatmentand/or diagnosis of testicular cancer. The testes are also a site ofactive gene expression of transcripts that may be expressed,particularly at low levels, in other tissues of the body. Therefore,this gene product may be expressed in other specific tissues or organswhere it may play related functional roles in other processes, such ashematopoiesis, inflammation, bone formation, and kidney function, toname a few possible target indications. Protein, as well as, antibodiesdirected against the protein may show utility as a tissue-specificmarker and/or immunotherapy target for the above listed tissues.

[0666] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:107 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1132 of SEQID NO:107, b is an integer of 15 to 1146, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:107, andwhere b is greater than or equal to a+14.

[0667] Features of Protein Encoded by Gene No: 98

[0668] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:LISSVNKTKQKRSDATLSHKHDRLLNHFVFFGNSYNY(SEQ ID NO: 565),SSKFPSDMLLRIQQIIYCHKLTIILTKWRNTARHKSKKKEDELILKHELQLKKWKNRLILKRAAAEESNFPERSSSEVFLVDETLKCDISLLPEXAILQVCMNSVYIIYYNLPSVVVHACNPSCLGG(SEQ ID NO: 566), SLESTNAIKSN (SEQ ID NO: 567), IRPNKNDQMRHCLINMIDY (SEQID NO: 568) ITLCFLETAITINIYSNLVNFLQICYCGYNRSSIVTS (SEQ ID NO: 569),and/or ISFRYAIADTTDHLLSQANHYPNKMAEYSKT (SEQ ID NO: 570). Polynucleotidesencoding these polypeptides are also encompassed by the invention.

[0669] This gene is expressed primarily in T-cells, tonsils, and hearttissue.

[0670] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of immunesystem and vascular tissue disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune system and vascular tissue, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., immune, vascular,cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0671] The tissue distribution in T-cells, tonsils and heart indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the diagnosis and treatment of disorders of the immune systemand vascular tissues. Expression of this gene product in tonsilsindicates a role in the regulation of the proliferation; survival;differentiation; and/or activation of potentially all hematopoietic celllineages, including blood stem cells. This gene product may be involvedin the regulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the gene or protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Therefore it may bealso used as an agent for immunological disorders including arthritis,asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoidarthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Inaddition, this gene product may have commercial utility in the expansionof stem cells and committed progenitors of various blood lineages, andin the differentiation and/or proliferation of various cell types.

[0672] Expression of this gene product in T cells also stronglyindicates a role for this protein in immune function and immunesurveillance. The tissue distribution in heart muscle tissue indicatesthat the protein product of this gene is useful for the diagnosis andtreatment of conditions and pathologies of the cardiovascular system,such as heart disease, restenosis, atherosclerosis, stoke, angina,thrombosis, and wound healing. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0673] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:108 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 761 of SEQID NO:108, b is an integer of 15 to 775, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:108, andwhere b is greater than or equal to a+14.

[0674] Features of Protein Encoded by Gene No: 99

[0675] An embodiment of the invention is directed to polypeptidescomprising those which exhibit sequence homology with honeybee venomsacepin. In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:PQIKLLNSDALGMRTTSXDLVPCNQCFIPLPPSCNRIASRKAVNWKQQRLPAVRGLLNNAPHRRPPTPRTPCVFPSEGPKGYGFHV(SEQ ID NO: 571), EQLAXISCRVINVSFRCLHHVIESLPERQLTGSSRGSQP (SEQ ID NO:572),EDCSTMPPIAAPPPLAPLVFSPLRGPRVMAFMSRCGDRGGRGRSXAGRGWPWSESGVINAHPKKRPCPGPMLS(SEQ ID NO: 573), and/orEFGTRRQWGTRCFPPLVGRKQSALRRREGKARAGRCCGKRSVKAGFDA (SEQ ID NO: 574).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0676] This gene is expressed primarily in activated and controlneutrophils, and to a lesser extent in fetal liver and spleen.

[0677] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdisorders of the immune and endocrine systems. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune, inflammatory and hormonal systems,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g., immune,cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0678] The tissue distribution in neutrophils and fetal liver and spleenindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the study, diagnosis and treatment of inflammationand various disorders of the immune and endocrine systems. This geneproduct may be involved in the regulation of cytokine production,antigen presentation, or other processes that may also suggest ausefulness in the treatment of cancer (e.g. by boosting immuneresponses). Since the gene is expressed in cells of lymphoid origin, thegene or protein, as well as, antibodies directed against the protein mayshow utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis.

[0679] In addition, this gene product may have commercial utility in theexpansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Expression of this gene product in neutrophils also stronglyindicates a role for this protein in immune function and immunesurveillance. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0680] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:109 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 897 of SEQID NO:109, b is an integer of 15 to 911, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:109, andwhere b is greater than or equal to a+14.

[0681] Features of Protein Encoded by Gene No: 100

[0682] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:AFFLLQALEIQSQLATPASSTARNPAPDLHHPHQPTIERFCRHSSSWERIEY (SEQ ID NO: 575).Polynucleotides encoding these polypeptides are also encompassed by theinvention. When tested against Jurkat T-cell lines, supernatants removedfrom cells containing this gene activated the GAS assay. Thus, it islikely that this gene activates T-cells through the Jak-STAT signaltransduction pathway. The gamma activating sequence (GAS) is a promoterelement found upstream of many genes which are involved in the Jak-STATpathway. The Jak-STAT pathway is a large, signal transduction pathwayinvolved in the differentiation and proliferation of cells. Therefore,activation of the Jak-STAT pathway, reflected by the binding of the GASelement, can be used to indicate proteins involved in the proliferationand differentiation of cells. Furthermore, contact of cells withsupernatant expressing the product of this gene increases thepermeability of Brian microvascular pericyte cells to calcium. Thus, itis likely that the product of this gene is involved in a signaltransduction pathway that is initiated when the product of this genebinds a receptor on the surface of the pericyte cell. Thus,polynucleotides and polypeptides have uses which include, but are notlimited to, activating pericyte (endothelial) cells.

[0683] This gene is expressed primarily in activated neutrophils.

[0684] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immunedisorders, inflammation. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0685] The tissue distribution in neutrophils and the biologicalactivity data suggest that polynucleotides and polypeptidescorresponding to this gene are useful for the study and treatment ofinflammatory and immune conditions. This gene product may be involved inthe regulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the gene or protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Therefore it may bealso used as an agent for immunological disorders including arthritis,asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoidarthritis, inflammatory bowel disease, sepsis, acne, and psoriasis.

[0686] In addition, this gene product may have commercial utility in theexpansion of stem cells and committed progenitors of various bloodlineages, and in the differentiation and/or proliferation of variouscell types. Expression of this gene product in neutrophils also stronglyindicates a role for this protein in immune function and immunesurveillance. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0687] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:110 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 442 of SEQID NO:110, b is an integer of 15 to 456, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:110, andwhere b is greater than or equal to a+14.

[0688] Features of Protein Encoded by Gene No: 101

[0689] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:ATVPGSIYNYFYHYNAGALKPEHASESPRGLCAQTAGPFPSF (SEQ ID NO: 576),IRHEPPPPRFKRFSCLSLLSSWDYRRAPPHVAIFCTLSRDGVLPHWPGWSQTPDLK (SEQ ID NO:577),STHLGLPRCWDYRHEPLCLAPFTTISIILMQGLSNLSMPQNPPEGCAHRLLDLSPASDSVPPEWGSKIAFEV(SEQ ID NO: 578), and/or LRVGGTSENCCRGECCGSVCIPPGRL (SEQ ID NO: 579).Polynucleotides encoding these polypeptides are also encompassed by theinvention. When tested against Jurkat T-cell lines, supernatants removedfrom cells containing this gene activated the GAS assay. Thus, it islikely that this gene activates T-cells through the Jak-STAT signaltransduction pathway. The gamma activating sequence (GAS) is a promoterelement found upstream of many genes which are involved in the Jak-STATpathway. The Jak-STAT pathway is a large, signal transduction pathwayinvolved in the differentiation and proliferation of cells. Therefore,activation of the Jak-STAT pathway, reflected by the binding of the GASelement, can be used to indicate proteins involved in the proliferationand differentiation of cells.

[0690] This gene is expressed primarily in neutrophils.

[0691] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immunedisorders. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0692] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study and treatment of immune disorders. Expression of this geneproduct in neutrophils also strongly indicates a role for this proteinin immune function and immune surveillance. This gene product may beinvolved in the regulation of cytokine production, antigen presentation,or other processes that may also suggest a usefulness in the treatmentof cancer (e.g. by boosting immune responses).

[0693] Since the gene is expressed in cells of lymphoid origin, the geneor protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. In addition, this geneproduct may have commercial utility in the expansion of stem cells andcommitted progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0694] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO: 111 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 540 of SEQID NO: 111, b is an integer of 15 to 554, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:111, andwhere b is greater than or equal to a+14.

[0695] Features of Protein Encoded by Gene No:102

[0696] This gene is expressed primarily in neutrophils.

[0697] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immuneconditions. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0698] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 251 as residues: Lys-33 to Lys-41.

[0699] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor study and treatment of immune disorders. This gene product may beinvolved in the regulation of cytokine production, antigen presentation,or other processes that may also suggest a usefulness in the treatmentof cancer (e.g. by boosting immune responses). Since the gene isexpressed in cells of lymphoid origin, the gene or protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis,acne, and psoriasis. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0700] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:112 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 708 of SEQID NO: 112, b is an integer of 15 to 722, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:112, andwhere b is greater than or equal to a+14.

[0701] Features of Protein Encoded by Gene No: 103

[0702] When tested against K562 leukemia cell lines, supernatantsremoved from cells containing this gene activated the ISRE assay. Thus,it is likely that this gene activates leukemia cells through theJak-STAT signal transduction pathway. The interferon-sensitive responseelement is a promoter element found upstream of many genes which areinvolved in the Jak-STAT pathway. The Jak-STAT pathway is a large,signal transduction pathway involved in the differentiation andproliferation of cells. Therefore, activation of the Jak-STAT pathway,reflected by the binding of the ISRE element, can be used to indicateproteins involved in the proliferation and differentiation of cells. Inspecific embodiments, polypeptides of the invention comprise thefollowing amino acid sequence: MCVTRMHVKCPPPSASVTAVKWPLSWSSSSFCISLHAGRH(SEQ ID NO: 580), and/or EERNKNHLSCQGLSTICCSYLSSKGEHLRNLSPYSF (SEQ IDNO: 581). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0703] This gene is expressed primarily in neutrophils.

[0704] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, immuneconditions. Similarly, polypeptides and antibodies directed to thesepolypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0705] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study and treatment of immune disorders. This gene product maybe involved in the regulation of cytokine production, antigenpresentation, or other processes that may also suggest a usefulness inthe treatment of cancer (e.g. by boosting immune responses). Since thegene is expressed in cells of lymphoid origin, the gene or protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis,acne, and psoriasis. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Expression of this gene product in neutrophilsalso strongly indicates a role for this protein in immune function andimmune surveillance. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0706] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:113 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 917 of SEQID NO:113, b is an integer of 15 to 931, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:113, andwhere b is greater than or equal to a+14.

[0707] Features of Protein Encoded by Gene No: 104

[0708] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:GLCMVHSLLTSSLGGRCCNYPYIADKDIETEVKPPSQGHTWHLHCS (SEQ ID NO: 582),QLWCITALPSTRHCSKGFAWFTHSLRHPSVAGAVIILILQTRTLRQRSSHLPKGTHGICTAPDRPTERAAVTILK(SEQ ID NO: 583), SFDNNNSYGVSQLYQVPDTVLRALHGSLTPYVIPRWQVL (SEQ ID NO:584), and/or DRGQATFPRAHMASALLLTDRQRELLSRSSNELCMSKV (SEQ ID NO: 585).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0709] This gene is expressed primarily in neutrophils.

[0710] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of immunediseases and disorders. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0711] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study and treatment of immune disorders. This gene product maybe involved in the regulation of cytokine production, antigenpresentation, or other processes that may also suggest a usefulness inthe treatment of cancer (e.g. by boosting immune responses). Since thegene is expressed in cells of lymphoid origin, the gene or protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis,acne, and psoriasis. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Expression of this gene product in neutrophilsalso strongly indicates a role for this protein in immune function andimmune surveillance. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0712] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:114 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 574 of SEQID NO:114, b is an integer of 15 to 588, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:114, andwhere b is greater than or equal to a+14.

[0713] Features of Protein Encoded by Gene No: 105

[0714] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:LLLILRPFLNSQFKLQLPLVLFHSSCTYICLLYNYELFHIVALTGKLMNLGLHLFAHHLILAVAHXGCSIPIY(SEQ ID NO: 586), and/or THNSNYSSLWFSSTAVVLTYVYYIIMNCFILSPLQVN (SEQ IDNO: 587). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0715] This gene is expressed primarily in neutrophils.

[0716] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of immunedisorders and diseases. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0717] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study and treatment of inflammatory and immune disorders. Thisgene product may be involved in the regulation of cytokine production,antigen presentation, or other processes that may also suggest ausefulness in the treatment of cancer (e.g. by boosting immuneresponses). Since the gene is expressed in cells of lymphoid origin, thegene or protein, as well as, antibodies directed against the protein mayshow utility as a tumor marker and/or immunotherapy targets for theabove listed tissues. Therefore it may be also used as an agent forimmunological disorders including arthritis, asthma, immune deficiencydiseases such as AIDS, leukemia, rheumatoid arthritis, inflammatorybowel disease, sepsis, acne, and psoriasis. In addition, this geneproduct may have commercial utility in the expansion of stem cells andcommitted progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Expressionof this gene product in neutrophils also strongly indicates a role forthis protein in immune function and immune surveillance. Protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.

[0718] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:115 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 798 of SEQID NO:115, b is an integer of 15 to 812, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:115, andwhere b is greater than or equal to a+14.

[0719] Features of Protein Encoded by Gene No: 106

[0720] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:TLVAGSPCSLSRWIMAGFCHGELVQSDMESQEWERGQVVLSHTSLPWCYVSPR (SEQ ID NO: 588),MAGFCHGELVQSDMESQEWERGQVVLSHTSLPWCYVSPR (SEQ ID NO: 589),MAVWISGSYSSFCSRSNWDVFSPNIVLASLPFSFRSVSKAAKPWWLALPALFPDGLWLDSAMGSLYSQTWKARNGKEVRWFSPTPHCLGAMSHL(SEQ ID NO: 590), and/or GWLYGSVGLIPHSAAEATG (SEQ ID NO: 591).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0721] This gene is expressed primarily in neutrophils.

[0722] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of immunedisorders and diseases. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0723] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 255 as residues: Pro-54 to Gly-62.

[0724] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study and treatment of immune disorders. This gene product maybe involved in the regulation of cytokine production, antigenpresentation, or other processes that may also suggest a usefulness inthe treatment of cancer (e.g. by boosting immune responses). Since thegene is expressed in cells of lymphoid origin, the gene or protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis,acne, and psoriasis. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Expression of this gene product in neutrophilsalso strongly indicates a role for this protein in immune function andimmune surveillance. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0725] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:116 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 492 of SEQID NO:116, b is an integer of 15 to 506, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:116, andwhere b is greater than or equal to a+14.

[0726] Features of Protein Encoded by Gene No: 107

[0727] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:RSKRQSQGSRCSVPLLAQQSRSPPVPLQAQPAWLLGSETIAWSGGGSGWEGPRDPGTSTAAGNSGPGIGMGHRTPPPSHTGR(SEQ ID NO: 592), RWDPAWGLDIPESSCPVTMGELRSGDGIVL (SEQ ID NO: 593),GALLWDNSMISAPRGSHREAGALFPSWLSNPAVLPSRSRPSQPGCLDPRQ (SEQ ID NO: 594),NSAREPRRWIRPTRGSGETTAPCCFEPLNGGTLVHAAAMARASEAAGTG (SEQ ID NO: 595),MARASEAAGTG (SEQ ID NO: 596),CFTTAFQKALRDPRPTLPDTHGSLRNAPLKSLTLPAAFVVSFFFLSLLQDGIKERSQTQNATFFFHDRSDIEGLSEEPCSGTTP(SEQ ID NO: 597),LALQEAVTGKQVLCSPPGSAIPQSSRPAPGPASLAAWIRDNSLVWRRLRVGGTQGPGHQYSSWEFRPRDRDGAQDTTPISHREMKVGSSMGTGHP(SEQ ID NO: 598), and/or MAGRLFTLLLWQELARRLVPGDASPRLSRKRSVTPGPPFPTLTVPSE(SEQ ID NO: 599). Polynucleotides encoding these polypeptides are alsoencompassed by the invention. When tested against sensory neuron celllines, supernatants removed from cells containing this gene activatedthe EGR1 assay. Thus, it is likely that this gene activates sensoryneuron cells through a signal transduction pathway. Early growthresponse 1 (EGR1) is a promoter associated with certain genes thatinduces various tissues and cell types upon activation, leading thecells to undergo differentiation and proliferation.

[0728] This gene is expressed primarily in neutrophils.

[0729] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of immunedisorders and diseases. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theimmune system, expression of this gene at significantly higher or lowerlevels may be routinely detected in certain tissues or cell types (e.g.,immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0730] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 256 as residues: Met-25 to Gly-30.

[0731] The tissue distribution in neutrophils indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study and treatment of immune disorders. This gene product maybe involved in the regulation of cytokine production, antigenpresentation, or other processes that may also suggest a usefulness inthe treatment of cancer (e.g. by boosting immune responses). Since thegene is expressed in cells of lymphoid origin, the gene or protein, aswell as, antibodies directed against the protein may show utility as atumor marker and/or immunotherapy targets for the above listed tissues.Therefore it may be also used as an agent for immunological disordersincluding arthritis, asthma, immune deficiency diseases such as AIDS,leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis,acne, and psoriasis. In addition, this gene product may have commercialutility in the expansion of stem cells and committed progenitors ofvarious blood lineages, and in the differentiation and/or proliferationof various cell types. Expression of this gene product in neutrophilsalso strongly indicates a role for this protein in immune function andimmune surveillance. Protein, as well as, antibodies directed againstthe protein may show utility as a tumor marker and/or immunotherapytargets for the above listed tissues.

[0732] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:117 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 737 of SEQID NO:117, b is an integer of 15 to 751, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:117, andwhere b is greater than or equal to a+14.

[0733] Features of Protein Encoded by Gene No: 108

[0734] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:MFYSKIFYFLLLNSDTSNNVTSKTLVSSISSSNNRLAVSIVF (SEQ ID NO: 600),SRQKNLLKLHSNPNCDNFCFIFNYKPKYICIFKLICLKILLYIFGSG (SEQ ID NO: 601), and/orMLLSLLMVFTSELYVKRHISFKSXDKPHCHKNQDIDVLFRKLLEKHFKVINMICFP (SEQ ID NO:602). Polynucleotides encoding these polypeptides are also encompassedby the invention.

[0735] This gene is expressed primarily in fetal liver, and to a lesserextent in bone and breast cancer cell lines.

[0736] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, cancerand metabolic disorders. Similarly, polypeptides and antibodies directedto these polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of thedigestive and skeletal system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., digestive, skeletal, cancerous and wounded tissues) orbodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0737] The tissue distribution in fetal liver/spleen, as well as boneand breast cancer, indicates that polynucleotides and polypeptidescorresponding to this gene are useful for study and treatment of growthand metabolic disorders and neoplasias (e.g. hepatoblastoma, jaundice,hepatitis, liver metabolic diseases and conditions that are attributableto the differentiation of hepatocyte progenitor cells). Furthermore, thetissue distribution indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the diagnosis and/or treatmentof bone and breast cancer, as well as cancers of other tissues whereexpression has been observed. The expression within fetal tissue andother cellular sources marked by proliferating cells suggests thisprotein may play a role in the regulation of cellular division, and mayshow utility in the diagnosis and treatment of cancer and otherproliferative disorders. Similarly, developmental tissues rely ondecisions involving cell differentiation and/or apoptosis in patternformation. Thus this protein may also be involved in apoptosis or tissuedifferentiation and could again be useful in cancer therapy. The proteinproduct of this clone is useful for the treatment and diagnosis ofhematopoietic related disorders such as anemia, pancytopenia,leukopenia, thrombocytopenia or leukemia since stromal cells areimportant in the production of cells of hematopoietic lineages. The usesinclude bone marrow cell ex-vivo culture, bone marrow transplantation,bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia.The gene product may also be involved in lymphopoiesis, therefore, itcan be used in immune disorders such as infection, inflammation,allergy, immunodeficiency etc. In addition, this gene product may havecommercial utility in the expansion of stem cells and committedprogenitors of various blood lineages, and in the differentiation and/orproliferation of various cell types. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0738] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:118 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 946 of SEQID NO:118, b is an integer of 15 to 960, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:118, andwhere b is greater than or equal to a+14.

[0739] Features of Protein Encoded by Gene No: 109

[0740] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: FREYGFYNLHFC (SEQ ID NO: 603),LVTTDYYDGCNEDYEYNWSYMFLNSEQLFIKFYPTFFC (SEQ ID NO: 604), and/orNVIAPGLESSCANSLFLLFVCLPVAHHRHNFLFIKHSLYNHLRDYESDFDKI (SEQ ID NO: 605).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0741] This gene is expressed primarily in T cells, fetal heart andinfant brain, and to a lesser extent in some transformed cell lines.

[0742] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of growthand immune disorders and diseases. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune and cardiovascular systems, expression ofthis gene at significantly higher or lower levels may be routinelydetected in certain tissues or cell types (e.g., immune, cardiovascular,cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum,plasma, urine, synovial fluid and spinal fluid) or another tissue orcell sample taken from an individual having such a disorder, relative tothe standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0743] The tissue distribution in immune cells, heart tissue, and braintissue indicates that polynucleotides and polypeptides corresponding tothis gene are useful for the study and treatment of developmental andimmune disorders. This gene product may be involved in the regulation ofcytokine production, antigen presentation, or other processes that mayalso suggest a usefulness in the treatment of cancer (e.g. by boostingimmune responses). Since the gene is expressed in cells of lymphoidorigin, the gene or protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues. Therefore it may be also used as an agentfor immunological disorders including arthritis, asthma, immunedeficiency diseases such as AIDS, leukemia, rheumatoid arthritis,inflammatory bowel disease, sepsis, acne, and psoriasis. In addition,this gene product may have commercial utility in the expansion of stemcells and committed progenitors of various blood lineages, and in thedifferentiation and/or proliferation of various cell types. Expressionof this gene product in T cells also strongly indicates a role for thisprotein in immune function and immune surveillance.

[0744] The tissue distribution in heart muscle tissue indicates that theprotein product of this gene is useful for the diagnosis and treatmentof conditions and pathologies of the cardiovascular system, such asheart disease, restenosis, atherosclerosis, stoke, angina, thrombosis,and wound healing. The tissue distribution in brain tissue indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the detection/treatment of neurodegenerative disease statesand behavioural disorders such as Alzheimers Disease, ParkinsonsDisease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania,dementia, paranoia, obsessive compulsive disorder, panic disorder,learning disabilities, ALS, psychoses, autism, and altered bahaviors,including disorders in feeding, sleep patterns, balance, and perception.In addition, the gene or gene product may also play a role in thetreatment and/or detection of developmental disorders associated withthe developing embryo, or sexually-linked disorders. Protein, as wellas, antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0745] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:119 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1428 of SEQID NO:119, b is an integer of 15 to 1442, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:119, andwhere b is greater than or equal to a+14.

[0746] Features of Protein Encoded by Gene No: 110

[0747] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: PKVLAVLKKKNHVALSIFELLSNDICSFISFFMS(SEQ ID NO: 606), EGPDINSNLKFLLCLKKKIMWPFQYLNC (SEQ ID NO: 607), and/orLLSLILLRIWYDFSKQTVFWFFLNVFNFFSSCNNDGACSYKYRKVQI (SEQ ID NO: 608).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0748] This gene is expressed primarily in osteoblasts, and to a lesserextent in bone marrow and bladder.

[0749] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, skeletaland hematopoietic diseases and disorders. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the skeletal and vascular systems, expression of thisgene at significantly higher or lower levels may be routinely detectedin certain tissues or cell types (e.g., skeletal, vascular, cancerousand wounded tissues) or bodily fluids (e.g., lymph, serum, plasma,urine, synovial fluid and spinal fluid) or another tissue or cell sampletaken from an individual having such a disorder, relative to thestandard gene expression level, i.e., the expression level in healthytissue or bodily fluid from an individual not having the disorder.

[0750] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 259 as residues: Gly-33 to Lys-38.

[0751] The tissue distribution in bone marrow and osteoblasts indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the study, diagnosis, and treatment of bone and hematopoieticdisorders. Elevated levels of expression of this gene product inosteoblasts indicates that it may play a role in the survival,proliferation, and/or growth of osteoblasts. Therefore, it may be usefulin influencing bone mass in such conditions as osteoporosis. Moregenerally, as evidenced by expression in bone marrow, this gene may playa role in the survival, proliferation, and/or differentiation ofhematopoietic cells in general, and may be of use in augmentation of thenumbers of stem cells and committed progenitors. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0752] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:120 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 831 of SEQID NO:120, b is an integer of 15 to 845, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:120, andwhere b is greater than or equal to a+14.

[0753] Features of Protein Encoded by Gene No: 111

[0754] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: HTLFISFLWAEG (SEQ ID NO: 609),MLPVFVLFFCFTYSARKQSVFKKGNVFE (SEQ ID NO: 610), and/orSPCSAAECHNLSLLSSCSLVSSNILFSFPFFGQKARCCLFLFYFSASHIAHESRVYSKKEMCL (SEQ IDNO: 611). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0755] This gene is expressed primarily in prostate cancer.

[0756] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, prostateand other cancers. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theendocrine system, expression of this gene at significantly higher orlower levels may be routinely detected in certain tissues or cell types(e.g., endocrine, cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0757] The tissue distribution in prostate cancer indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the study and treatment of prostate cancer, as well as cancers ofother tissues where expression has been observed. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0758] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:121 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 346 of SEQID NO:121, b is an integer of 15 to 360, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:121, andwhere b is greater than or equal to a+14.

[0759] Features of Protein Encoded by Gene No: 112

[0760] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:HKCFQCFILANGFLKVIKPFQRNWSDKTFFLVCLNKAISEALLSKMTFLSFFKTNLLLLETFCTI (SEQID NO: 612),LLGVLKPLYFSVEPVLGERSVAFEEVREKNHGTSGFLSLYSLAAIVCGHLMFFHTLLGRGGNDHPGQSPLPGMRPLRGGLAGQAPSGHPWMQPLDTCLL(SEQ ID NO: 613), RPTRPPTRPDRPSLELAPGLCADFLGSSNHCIFLLSLYLGRDQ (SEQ IDNO: 614), and/or EKRIMVPQGFFPFTRWQPLSVGTSCFSTLYWAVEVTITQASLLCLGCAL (SEQID NO: 615). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0761] This gene is expressed primarily in haemopoietic and neuraltissues, and to a lesser extent in a number of cancers and othertissues.

[0762] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the haemopoietic and neural systems. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the immune and neural system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., immune, neural, cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0763] The tissue distribution in immune and neural tissues indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the diagnosis and treatment of diseases of the haemopoieticand neural systems, including several cancers. This gene product may beinvolved in the regulation of cytokine production, antigen presentation,or other processes that may also suggest a usefulness in the treatmentof cancer (e.g. by boosting immune responses). Since the gene isexpressed in cells of lymphoid origin, the gene or protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.Therefore it may be also used as an agent for immunological disordersincluding arthritis. asthma, immune deficiency diseases such as AIDS,leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis,acne, and psoriasis.

[0764] In addition, this gene product may have commercial utility in theexpansion of stem cells and committed progenitors of various bloodlineages. and in the differentiation and/or proliferation of variouscell types. Furthermore, the tissue distribution indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the detection/treatment of neurodegenerative disease states andbehavioural disorders such as Alzheimers Disease, Parkinsons Disease,Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia,paranoia, obsessive compulsive disorder, panic disorder, learningdisabilities, ALS, psychoses, autism, and altered bahaviors, includingdisorders in feeding, sleep patterns, balance, and perception. Inaddition, the gene or gene product may also play a role in the treatmentand/or detection of developmental disorders associated with thedeveloping embryo, or sexually-linked disorders. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0765] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:122 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 930 of SEQID NO:122, b is an integer of 15 to 944, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:122, andwhere b is greater than or equal to a+14.

[0766] Features of Protein Encoded by Gene No: 113

[0767] The translation product of this gene shares sequence homologywith intestinal epithelium proliferating cell-associated mRNA sequence,which is thought to be important in the growth and development ofepithelial cells. In specific embodiments, polypeptides of the inventioncomprise the following amino acid sequence:MTLDEWKNLQEQTRPKPEFNIRKPESTVPSKAVVIRESKYRDDMVKDDYEDDSHVFRKPANDITSQLEINFGNLPRPGRGARGGTRGGRGRIRRAENYGPRAEVVMQDVAPNPDDPEDFPALS(SEQ ID NO: 616),CKMLPPTQMTRKISLRCLERALFPSTAELHCTPVGRLFQLGQGSQTLRTIDVAFPVSCKFVALFWAELLEGLLQRLESRPFPKKMKNGDCVFIEGISNEE(SEQ ID NO: 617), PPSSWAWSQRRHPGRPGKDQEGRELWTQSRSGDARCCPQPR (SEQ ID NO:618), and/or CLKCVYRDSIDSSAEAWRERRL (SEQ ID NO: 619). Polynucleotidesencoding these polypeptides are also encompassed by the invention.

[0768] This gene is expressed primarily in brain and central nervoussystem tissues, such as the frontal cortex, amygdala, and hypothalmus,and to a lesser extent in testis.

[0769] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the neural system. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). For anumber of disorders of the above tissues or cells, particularly of theneural and reproductive system, expression of this gene at significantlyhigher or lower levels may be routinely detected in certain tissues orcell types (e.g., neural, reproductive, cancerous and wounded tissues)or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid andspinal fluid) or another tissue or cell sample taken from an individualhaving such a disorder, relative to the standard gene expression level,i.e., the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0770] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 262 as residues: Glu-20 to Glu-27, Glu-30 to Trp-44.

[0771] The tissue distribution and homology to intestinal epitheliumproliferating cell-associated mRNA sequence indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor growth and developmental diseases of the brain, central nervoussystem and reproductive system. The tissue distribution in neuraltissues indicates that polynucleotides and polypeptides corresponding tothis gene are useful for the detection/treatment of neurodegenerativedisease states and behavioural disorders such as Alzheimers Disease,Parkinsons Disease, Huntingtons Disease, Tourette Syndrome,schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder,panic disorder, learning disabilities, ALS, psychoses, autism, andaltered bahaviors, including disorders in feeding, sleep patterns,balance, and perception.

[0772] In addition, the gene or gene product may also play a role in thetreatment and/or detection of developmental disorders associated withthe developing embryo, or sexually-linked disorders. Elevated expressionof this gene product within the frontal cortex of the brain indicatesthat it may be involved in neuronal survival; synapse formation;conductance; neural differentiation, etc. Such involvement may impactmany processes, such as learning and cognition. Protein, as well as,antibodies directed against the protein may show utility as a tumormarker and/or immunotherapy targets for the above listed tissues.

[0773] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:123 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 900 of SEQID NO:123, b is an integer of 15 to 914, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:123, andwhere b is greater than or equal to a+14.

[0774] Features of Protein Encoded by Gene No: 114

[0775] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: LSYSVLLILPLFHSLPTLKDTHTHNKWVE (SEQ IDNO: 620), EVNGVGYKHSCFSDISSVLENKDSRMRAPHYASFQHFFSVLLKLSPQACLTESQCIPLTFY(SEQ ID NO: 621), KTHTHTISGWSKKSTELDISIPAFLTSPVSWRTRILE (SEQ ID NO:622), and/or IRHELGSSDPPAEASQIAGTAAVSHHAQP (SEQ ID NO: 623).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0776] This gene is expressed primarily in spinal cord.

[0777] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, spinalcord injuries and diseases of the neural system. Similarly, polypeptidesand antibodies directed to these polypeptides are useful in providingimmnunological probes for differential identification of the tissue(s)or cell type(s). For a number of disorders of the above tissues orcells, particularly of the neural system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., neural, cancerous and woundedtissues) or bodily fluids (e.g., lymph, serim, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0778] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 263 as residues: Pro-45 to Gln-52.

[0779] The tissue distribution in spinal cord indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis and treatment of spinal cord injuries and diseases ofthe neural system, such as spinal deformation, spinocerebullar ataxiatypes I and III, dentatorubropallidoluysian and spinal bulbar muscularatrophy. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0780] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:124 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 448 of SEQID NO:124, b is an integer of 15 to 462, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:124, andwhere b is greater than or equal to a+14.

[0781] Features of Protein Encoded by Gene No: 115

[0782] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: MLYLILISLSSLSFSFSLPPFSIII (SEQ ID NO:624), SSYFLRHFRIYHTCPKYFSMNIIN (SEQ ID NO: 625),KLTLTKGNKSWSSTAVAAALELVDPPGCRNSARDSLPNSTM MFYYACFILYSSLSPLSLSLSPSLLSLL(SEQ ID NO: 626), and/or QFHTGNSYDHDYAK (SEQ ID NO: 627).Polynucleotides encoding these polypeptides are also encompassed by theinvention. When tested against U937 Myeloid cell lines, supernatantsremoved from cells containing this gene activated the GAS assay. Thus,it is likely that this gene activates myeloid cells through the Jak-STATsignal transduction pathway. The gamma activating sequence (GAS) is apromoter element found upstream of many genes which are involved in theJak-STAT pathway. The Jak-STAT pathway is a large, signal transductionpathway involved in the differentiation and proliferation of cells.Therefore, activation of the Jak-STAT pathway, reflected by the bindingof the GAS element, can be used to indicate proteins involved in theproliferation and differentiation of cells.

[0783] This gene is expressed primarily in striatum.

[0784] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of anumber of diseases of the neural system. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the neural diseases, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., striatum, cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0785] The tissue distribution in striatum indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the diagnosis and treatment of diseases of the neural system.Furthermore, the tissue distribution indicates that polynucleotides andpolypeptides corresponding to this gene are useful for thedetection/treatment of neurodegenerative disease states and behaviouraldisorders such as Alzheimers Disease, Parkinsons Disease, HuntingtonsDisease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia,obsessive compulsive disorder, panic disorder, learning disabilities,ALS, psychoses, autism, and altered bahaviors, including disorders infeeding, sleep patterns, balance, and perception. In addition, the geneor gene product may also play a role in the treatment and/or detectionof developmental disorders associated with the developing embryo, orsexually-linked disorders. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0786] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:125 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 531 of SEQID NO:125, b is an integer of 15 to 545, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:125, andwhere b is greater than or equal to a+14.

[0787] Features of Protein Encoded by Gene No: 116

[0788] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: AVCTGGYCESCRCEHCVCVCVDLCVLFSGKELRVR(SEQ ID NO: 628), VSFFFVFKWSFAEIKSREEHWASLTPKPTLLSALLTCDVLKSSIIFKCCESTEDKGFDSFFQASKDGSSSRI (SEQ ID NO:629),RSWGSQRSLCLLFIPFAAESYSVVWMGHLFVVCLLSSWWTFRPFALAVTVNHVAVNIVCVSAWTCVSCSLGRSCGLEGSFLFPLETLWFPHMVVLCLTF(SEQ ID NO: 630),MGHLFVVCLLSSWWTFRPFALAVTVNHVAVNIVCVSAWTCVSCSLGRSCGLEGSFLFPLETLWFPHMVVLCLTF(SEQ ID NO: 631), HDVLGARNAACVCCSFLLQQNRILLFGWATCLLSVYSPAGGHLGRLHWRLL(SEQ ID NO: 632),MLDFKTSQVSKALKRVGFGVRLAQCSSLDLISAKLHLKTKKKETYITSTVMTAASLFLSYVTSEFTRSIMATFYCFVLKLHIGEMGTLQTAGGSKMTWPLQKAIWQFLKRLSIKLPYVETRESPGETKNY (SEQ ID NO: 633), and/orLTRNSFPENRTHKSTQTHTQCSQRHDSQ (SEQ ID NO: 634). Polynucleotides encodingthese polypeptides are also encompassed by the invention.

[0789] This gene is expressed primarily in intestine and cancer cells.

[0790] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the gastrointestinal tract and cancer. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the digestive system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., digestive, cancerous and woundedtissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovialfluid and spinal fluid) or another tissue or cell sample taken from anindividual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0791] The tissue distribution in gastrointestinal tissues and canceroustissues indicates that polynucleotides and polypeptides corresponding tothis gene are useful for the treatment and diagnosis of diseases of thedigestive system and cancer. Furthermore, the tissue distribution ingastrointestinal tissues indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the diagnosis, prevention,and/or treatment of various metabolic disorders such as Tay-Sachsdisease, phenylkenonuria, galactosemia, porphyrias, and Hurler'ssyndrome. Protein, as well as, antibodies directed against the proteinmay show utility as a tumor marker and/or immunotherapy targets for theabove listed tissues.

[0792] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:126 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 898 of SEQID NO:126, b is an integer of 15 to 912, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:126, andwhere b is greater than or equal to a+14.

[0793] Features of Protein Encoded by Gene No: 117

[0794] The translation product of this gene shares sequence homologywith a human apoptosis regulating protein which is thought to beimportant in regulating cell death. In specific embodiments,polypeptides of the invention comprise the following amino acidsequence:IRHEGQSSSRGSSHCDSPSPQEDGQIMFDVEMHTSRDHSSQSEEEVVEGEKEVEALKKSADWVSDWSSRPENIPPKEFHFRHPKRSVSLS(SEQ ID NO: 635), GILLTLYPFWPEDILEFPNRVYCCLEICKGFFSANATSRL (SEQ ID NO:636), EFGTRDRVVPEAVLTVTALRHKKMGRSCLMWKCTPAGTIALSQKKKL (SEQ ID NO: 637),AHPLPAPTEGKEKPLEMRVTCEVVYCHSSLFELETIVSMTQPTTLFLHIQFQ (SEQ ID NO: 638),TFCVFKHEEKWSHEERGYFLRRISEGVHSISLPFSCFGFGARHLYWKATEHTLCQHLLRERKSPWKCV(SEQ ID NO: 639), and/orQSLLLFRNLQGLLFRKCHQQIIILSAMLLSLISATRLDLYHSWYKFYSCNITTISLLKRDQVSK (SEQ IDNO: 640). Polynucleotides encoding these polypeptides are alsoencompassed by the invention. When tested against Jurkat cell lines,supernatants removed from cells containing this gene activated the NF-kBtranscription factor. Thus, it is likely that this gene activates Jurkatcells by activating a transcriptional factor found within these cells.Nuclear factor kB is a transcription factor activated by a wide varietyof agents, leading to cell activation, differentiation, or apoptosis.Reporter constructs utilizing the NF-kB promoter element are used toscreen supernatants for such activity.

[0795] This gene is expressed primarily in muscle, fibroblast cells,haemopoietic cells, and fetal lung.

[0796] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the haemopoietic, muscular and developing systems. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune and muscular system,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g., immune,muscular, cancerous and wounded tissues) or bodily fluids (e.g., lymph,serum, plasma, urine, synovial fluid and spinal fluid) or another tissueor cell sample taken from an individual having such a disorder, relativeto the standard gene expression level, i.e., the expression level inhealthy tissue or bodily fluid from an individual not having thedisorder.

[0797] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 266 as residues: Met-i to Ala-6.

[0798] The tissue distribution in muscle and homology to apoptosisregulating protein indicates that polynucleotides and polypeptidescorresponding to this gene are useful for diagnosis and treatment ofdiseases of the haemopoietic, muscular and developing systems.Expression within embryonic tissue and other cellular sources marked byproliferating cells indicates that this protein may play a role in theregulation of cellular division. Additionally, the expression inhematopoietic cells and tissues indicates that this protein may play arole in the proliferation, differentiation, and/or survival ofhematopoietic cell lineages. In such an event, this gene may be usefulin the treatment of lymphoproliferative disorders, and in themaintenance and differentiation of various hematopoietic lineages fromearly hematopoietic stem and committed progenitor cells. Similarly,embryonic development also involves decisions involving celldifferentiation and/or apoptosis in pattern formation. Thus this proteinmay also be involved in apoptosis or tissue differentiation and couldagain be useful in cancer therapy. Protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0799] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:127 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1034 of SEQID NO:127, b is an integer of 15 to 1048, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:127, andwhere b is greater than or equal to a+14.

[0800] Features of Protein Encoded by Gene No: 118

[0801] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: IRHEESFNPLTCGFSLFFSLFS (SEQ ID NO:641), METLLLLLFFLSLLIFRFRILVSQCIN (SEQ ID NO: 642),FLLTTVLLFSSKVRDPRANFDQSLRVLKHAKKVQPDVISKTSIMLGLGENDEQVYATMKGKEEK (SEQ IDNO: 643), and/or QQSCCFPVRFVILGPILISPYVY (SEQ ID NO: 644).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0802] This gene is expressed primarily in synovium.

[0803] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, arthritisand other diseases of the musculo-skeletal system . Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the musculo-skeletal system,expression of this gene at significantly higher or lower levels may beroutinely detected in certain tissues or cell types (e.g.,musculo-skeletal, cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0804] The tissue distribution in synovium indicates thatpolynucleotides and polypeptides corresponding to this gene are usefulfor the treatment and diagnosis of diseases of the muscular-skeletalsystem. Furthermore, the expression of this gene product in synoviumindicates a role in the detection and treatment of disorders andconditions affecting the skeletal system, in particular osteoporosis aswell as disorders afflicting connective tissues (e.g. arthritis, trauma,tendonitis, chrondomalacia and inflammation), such as in the diagnosisor treatment of various autoimmune disorders such as rheumatoidarthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism,spinal deformation, and specific joint abnormalities as well aschondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familialosteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasiatype Schmid). Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0805] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:128 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 708 of SEQID NO:128, b is an integer of 15 to 722, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:128, andwhere b is greater than or equal to a+14.

[0806] Features of Protein Encoded by Gene No: 119

[0807] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:VWLLSSILLRVLWNRYTLQELSFWLPWFASRATSLVLQHGDNYLLFLFCFVCFVLAMPF (SEQ ID NO:645), IRHEVSMAFVFHLAQGTLEPLYIAGA (SEQ ID NO: 646),NSARGEYGFCLPSCSGYFGTAIHCRSLASGYHGLLPEQQA (SEQ ID NO: 647), and/orHELTVPSRMGSKGKPYPCGFYSSLIP (SEQ ID NO: 648). Polynucleotides encodingthese polypeptides are also encompassed by the invention. When testedagainst U937 Myeloid cell lines, supernatants removed from cellscontaining this gene activated the GAS assay. Thus, it is likely thatthis gene activates myeloid cells through the Jak-STAT signaltransduction pathway. The gamma activating sequence (GAS) is a promoterelement found upstream of many genes which are involved in the Jak-STATpathway. The Jak-STAT pathway is a large, signal transduction pathwayinvolved in the differentiation and proliferation of cells. Therefore,activation of the Jak-STAT pathway, reflected by the binding of the GASelement, can be used to indicate proteins involved in the proliferationand differentiation of cells.

[0808] This gene is expressed primarily in rejected kidney, stromalcells, and infant brain.

[0809] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the renal, central nervous and immune systems. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune, renal and central nervoussystem, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,immune, renal, nervous, cancerous and wounded tissues) or bodily fluids(e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid) oranother tissue or cell sample taken from an individual having such adisorder, relative to the standard gene expression level, i.e., theexpression level in healthy tissue or bodily fluid from an individualnot having the disorder.

[0810] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 268 as residues: Ser-6 to Arg-15.

[0811] The tissue distribution rejected kidney, stromal cells, andinfant brain indicates that polynucleotides and polypeptidescorresponding to this gene are useful for the diagnosis and treatment ofdiseases of the renal, central nervous, and immune systems. The tissuedistribution in infant brain indicates that polynucleotides andpolypeptides corresponding to this gene are useful for thedetection/treatment of neurodegenerative disease states and behaviouraldisorders such as Alzheimers Disease, Parkinsons Disease, HuntingtonsDisease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia,obsessive compulsive disorder, panic disorder, learning disabilities,ALS, psychoses, autism, and altered bahaviors, including disorders infeeding, sleep patterns, balance, and perception. In addition, the geneor gene product may also play a role in the treatment and/or detectionof developmental disorders associated with the developing embryo, orsexually-linked disorders.

[0812] Alternatively, this gene product may be involved in theregulation of cytokine production, antigen presentation, or otherprocesses that may also suggest a usefulness in the treatment of cancer(e.g. by boosting immune responses). Since the gene is expressed incells of lymphoid origin, the gene or protein, as well as, antibodiesdirected against the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues. Therefore it may bealso used as an agent for immunological disorders including arthritis,asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoidarthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. Inaddition, this gene product may have commercial utility in the expansionof stem cells and committed progenitors of various blood lineages, andin the differentiation and/or proliferation of various cell types.

[0813] The tissue distribution in kidney indicates that this gene orgene product is useful in the treatment and/or detection of kidneydiseases including renal failure, nephritus, renal tubular acidosis,proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephroticsyndrome, crush syndrome, glomerulonephritis, hematuria, renal colic andkidney stones, in addition to Wilm's Tumor Disease, and congenitalkidney abnormalities such as horseshoe kidney, polycystic kidney, andFalconi's syndrome. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0814] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:129 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 463 of SEQID NO:129, b is an integer of 15 to 477, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:129, andwhere b is greater than or equal to a+14.

[0815] Features of Protein Encoded by Gene No: 120

[0816] The protein of the invention has sequence identity to theSaccharomyces cerevisiae ankyrin repeat-containing protein (gi|466522).The translation product of this gene also shares homology with C.elegans protein C43H6.7 gene product (Genbank Accession No. gi|1255324).In specific embodiments, polypeptides of the invention comprise thefollowing amino acid sequence:KCIYPKPARTHHCSICNRCVLKIMDHHCPWLNNCVGHYNHRYFFSFCFFMTLGCVYCSYGSWDLFREAYAAIEKMKQLDKNKLQAVANQTYHQTPPPTFSFRER(SEQ ID NO: 649), ARGHWNLLIVFHYYQAITTPPGYPPQGRNDIATVSIC (SEQ ID NO:650), WQCELDCVSHDSSTHSAPYVISRASKGSFSQNP (SEQ ID NO: 651),SKRASGPALGYHAGQFKDQPFYHCRRKTQCGEILGLTSLYSGKQKFQPQTRGQAASYLPCPVLTRTSSRIQHWSWPPPLLLAV(SEQ ID NO: 652), ESLQLRLLGQLEGIPGCGYRKALAYSGALTF (SEQ ID NO: 653),and/orSLAPWEWNELGAPSLGDCSLSLCDGSVSWTVSATTRALILLPMLFQGPPRAAFLRILDQKEPVGLP (SEQID NO: 654). Polynucleotides encoding these polypeptides are alsoencompassed by the invention.

[0817] This gene is expressed primarily in endometrial tumor, colontumor, prostate cancer, and ovarian cancer.

[0818] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis of anumber of types of cancers, particularly endometrial, prostate, ovarian,and colon cancers. Similarly, polypeptides and antibodies directed tothese polypeptides are useful in providing immunological probes fordifferential identification of the tissue(s) or cell type(s). Fora,number of disorders of the above tissues or cells, particularly of theendometrium, prostate, colon, and ovary, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., prostate, colon, ovary,endometrium, cancerous and wounded tissues) or bodily fluids (e.g.,lymph, serum, plasma, urine, synovial fluid and spinal fluid) or anothertissue or cell sample taken from an individual having such a disorder,relative to the standard gene expression level, i.e., the expressionlevel in healthy tissue or bodily fluid from an individual not havingthe disorder.

[0819] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 269 as residues: Asn-43 to Arg-49, Phe-57 to Cys-65, Pro-93to Ser-99.

[0820] The tissue distribution in prostate cancer, ovarian cancer, coloncancer, and endometrial cancer tissues indicates that polynucleotidesand polypeptides corresponding to this gene are useful for the diagnosisand treatment of diseases and cancers of the prostate, ovaries, colon,and endometrium, as well as cancers of other tissues where expressionhas been observed. Expression within cellular sources marked byproliferating cells suggests this protein may play a role in theregulation of cellular division, and may show utility in the diagnosisand treatment of cancer and other proliferative disorders. Similarly,developmental tissues rely on decisions involving cell differentiationand/or apoptosis in pattern formation. Thus this protein may also beinvolved in apoptosis or tissue differentiation and could again beuseful in cancer therapy. Protein, as well as, antibodies directedagainst the protein may show utility as a tumor marker and/orimmunotherapy targets for the above listed tissues.

[0821] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:130 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 1282 of SEQID NO:130, b is an integer of 15 to 1296, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:130, andwhere b is greater than or equal to a+14.

[0822] Features of Protein Encoded by Gene No: 121

[0823] The translation product of this gene shares sequence homologywith adrenalin receptor (Patent serial No. J08126491-A.) In specificembodiments, polypeptides of the invention comprise the following aminoacid sequence:TATLNSFFGGWGLALLLRLECSDTIMDHCSLDLLGSSNPPASASQVVGTTGARHHAQLIFCFFVQTRSHSVA(SEQ ID NO: 655), MDHCSLDLLGSSNPPASASQVVGTTGARHHAQLIFCFFVQTRSHSVA (SEQID NO: 656), GVLKQSSHLVLSKG (SEQ ID NO: 657), DYSCESLCPALLSIAPDIVLN (SEQID NO: 658), TTIHKTQLGSYKILWEPKEGYHNSTWI (SEQ ID NO: 659), IREIFLRRP(SEQ ID NO: 660), and/or LKFQKPGKIQMRGGGRVFWYKNCK (SEQ ID NO: 661).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0824] This gene is expressed primarily in synovial sarcoma.

[0825] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, arthritisand other diseases of the synovium including cancers. Similarly,polypeptides and antibodies directed to these polypeptides are useful inproviding immunological probes for differential identification of thetissue(s) or cell type(s). For a number of disorders of the abovetissues or cells, particularly of the immune and muscular-skeletalsystem, expression of this gene at significantly higher or lower levelsmay be routinely detected in certain tissues or cell types (e.g.,immune, musculo-skeletal, cancerous and wounded tissues) or bodilyfluids (e.g., lymph, serum, plasma, urine, synovial fluid and spinalfluid) or another tissue or cell sample taken from an individual havingsuch a disorder, relative to the standard gene expression level, i.e.,the expression level in healthy tissue or bodily fluid from anindividual not having the disorder.

[0826] The tissue distribution in synovial sarcoma tissue and thehomology to adrenalin receptor indicates that polynucleotides andpolypeptides corresponding to this gene are useful for the diagnosis andtreatment of diseases of the synovium, immune system andmusculo-skeletal system including cancers of these tissues and systems.It may also be useful for identifying and therapeutically usingantagonists and agonists for this receptor family. In addition, theexpression of this gene product in synovium indicates a role in thedetection and treatment of disorders and conditions affecting theskeletal system, in particular osteoporosis as well as disordersafflicting connective tissues (e.g. arthritis, trauma, tendonitis,chrondomalacia and inflammation), such as in the diagnosis or treatmentof various autoimmune disorders such as rheumatoid arthritis, lupus,scleroderma, and dermatomyositis as well as dwarfism, spinaldeformation, and specific joint abnormalities as well aschondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familialosteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasiatype Schmid). Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0827] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:131 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 724 of SEQID NO:131, b is an integer of 15 to 738, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:131, andwhere b is greater than or equal to a+14.

[0828] Features of Protein Encoded by Gene No: 122

[0829] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence: NSARVTQKGESVGSVGCMRAIAGFDNYPLF (SEQID NO: 662), GTIGIFWPLPVAILSSGDYLQTQIHRPLLHRGT (SEQ ID NO: 663),LPLPLSSLLHIATCNPFPKT (SEQ ID NO: 664),SYFFVYNLILKIIQGDHASIILLATIPIFGDIYYVKGQLASFGPYL (SEQ ID NO: 665),LFYHLEIISRHKSIAHCSIEA (SEQ ID NO: 666), CSCHCPSRAFST (SEQ ID NO: 667),and/or PHAIHSQKPSSIFLITDVFPDPPVGIYLL (SEQ ID NO: 668). Polynucleotidesencoding these polypeptides are also encompassed by the invention.

[0830] This gene is expressed primarily in chronic synovitis.

[0831] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to,inflammatory diseases and disorders of the musculo-skeletal system.Similarly , polypeptides and antibodies directed to these polypeptidesare useful in providing immunological probes for differentialidentification of the tissue(s) or cell type(s). For a number ofdisorders of the above tissues or cells, particularly of theinflammatory and musculo-skeletal system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., musculo-skeletal, cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0832] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 271 as residues: Ser-39 to Pro-44.

[0833] The tissue distribution in chronic synovitis tissue indicatesthat polynucleotides and polypeptides corresponding to this gene areuseful for the treatment and diagnosis of disorders and diseases of theinflammatory and musculo-skeletal system. In addition, the expression ofthis gene product in synovium indicates a role in the detection andtreatment of disorders and conditions affecting the skeletal system, inparticular osteoporosis as well as disorders afflicting connectivetissues (e.g. arthritis, trauma, tendonitis, chrondomalacia andinflammation), such as in the diagnosis or treatment of variousautoimmune disorders such as rheumatoid arthritis, lupus, scleroderma,and dermatomyositis as well as dwarfism, spinal deformation, andspecific joint abnormalities as well as chondrodysplasias (ie.spondyloepiphyseal dysplasia congenita, familial osteoarthritis,Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).Protein, as well as, antibodies directed against the protein may showutility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.

[0834] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:132 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 428 of SEQID NO:132, b is an integer of 15 to 442, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:132, andwhere b is greater than or equal to a+14.

[0835] Features of Protein Encoded by Gene No: 123

[0836] In specific embodiments, polypeptides of the invention comprisethe following amino acid sequence:RKLFHKINSKSFHLSGMHILISVWIVRSRIIKVKYELLLCFFDVIFYV (SEQ ID NO: 669),NSARDVFFTQKILYSQTCIFFPCLVPFSFLFSFFFFLSFVG (SEQ ID NO: 670),MFSSLKKFYILKHVYSFPVLFHFLFFFLFSFSFLSWAEKGAGKMKLATENCKMVKS (SEQ ID NO:671), and/or IQLLYLKGAAMKYLSYVARLLFLKALDLFAPKMVQIDSF (SEQ ID NO: 672).Polynucleotides encoding these polypeptides are also encompassed by theinvention.

[0837] This gene is expressed primarily in kidney and infant brain.

[0838] Therefore, polynucleotides and polypeptides of the invention areuseful as reagents for differential identification of the tissue(s) orcell type(s) present in a biological sample and for diagnosis ofdiseases and conditions which include, but are not limited to, diseasesof the renal and central nervous systems. Similarly, polypeptides andantibodies directed to these polypeptides are useful in providingimmunological probes for differential identification of the tissue(s) orcell type(s). For a number of disorders of the above tissues or cells,particularly of the neural and renal system, expression of this gene atsignificantly higher or lower levels may be routinely detected incertain tissues or cell types (e.g., neural, renal, cancerous andwounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine,synovial fluid and spinal fluid) or another tissue or cell sample takenfrom an individual having such a disorder, relative to the standard geneexpression level, i.e., the expression level in healthy tissue or bodilyfluid from an individual not having the disorder.

[0839] Preferred epitopes include those comprising a sequence shown inSEQ ID NO. 272 as residues: Gly-24 to Lys-31.

[0840] The tissue distribution in kidney and infant brain tissuesindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the diagnosis and treatment of diseases of theneural and renal systems. The tissue distribution in infant brainindicates that polynucleotides and polypeptides corresponding to thisgene are useful for the detection/treatment of neurodegenerative diseasestates and behavioural disorders such as Alzheimers Disease, ParkinsonsDisease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania,dementia, paranoia, obsessive compulsive disorder, panic disorder,learning disabilities, ALS, psychoses, autism, and altered bahaviors,including disorders in feeding, sleep patterns, balance, and perception.In addition, the gene or gene product may also play a role in thetreatment and/or detection of developmental disorders associated withthe developing embryo, or sexually-linked disorders.

[0841] The tissue distribution in kidney indicates that this gene orgene product is useful in the treatment and/or detection of kidneydiseases including renal failure, nephritus, renal tubular acidosis,proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephroticsyndrome, crush syndrome, glomerulonephritis, hematuria, renal colic andkidney stones, in addition to Wilm's Tumor Disease, and congenitalkidney abnormalities such as horseshoe kidney, polycystic kidney, andFalconi's syndrome. Protein, as well as, antibodies directed against theprotein may show utility as a tumor marker and/or immunotherapy targetsfor the above listed tissues.

[0842] Many polynucleotide sequences, such as EST sequences, arepublicly available and accessible through sequence databases. Some ofthese sequences are related to SEQ ID NO:133 and may have been publiclyavailable prior to conception of the present invention. Preferably, suchrelated polynucleotides are specifically excluded from the scope of thepresent invention. To list every related sequence would be cumbersome.Accordingly, preferably excluded from the present invention are one ormore polynucleotides comprising a nucleotide sequence described by thegeneral formula of a−b, where a is any integer between 1 to 868 of SEQID NO:133, b is an integer of 15 to 882, where both a and b correspondto the positions of nucleotide residues shown in SEQ ID NO:133, andwhere b is greater than or equal to a+14. 5′ NT NT of AA First Last ATCCSEQ 5′ NT 3′ NT 5′ NT First SEQ AA AA First AA Last Deposit ID Total ofof of AA of ID of of of AA Gene cDNA Nr and NO: NT Clone Clone StartSignal NO: Sig Sig Secreted of No. Clone ID Date Vector X Seq. Seq. Seq.Codon Pep Y Pep Pep Portion ORF 1 HCEIA77 209119 Uni-ZAP XR 11 1882 6761882 785 785 150 1 37 38 53 06/12/97 2 HCFCE10 209119 pSport1 12 1590 181590 198 198 151 1 19 20 45 06/12/97 3 HCFNC26 209119 pSport1 13 1373 61373 85 85 152 1 18 19 24 06/12/97 4 HCHAA63 209119 pSport1 14 1142 11142 130 130 153 1 37 38 264 06/12/97 5 HCNSP40 209119 pBluescript 151034 1 1034 106 106 154 1 19 20 237 06/12/97 5 HCNSP40 209119pBluescript 134 1032 1 1032 111 273 1 14 06/12/97 6 HDAAC10 209119pSport1 16 1198 1 1198 117 117 155 1 21 22 313 06/12/97 7 HE8CV18 209119Uni-ZAP XR 17 1447 1 1447 176 176 156 1 29 30 98 06/12/97 8 HELDY05209119 Uni-ZAP XR 18 1422 1 1375 79 79 157 1 34 35 36 06/12/97 9 HELDZ32209119 Uni-ZAP XR 19 1107 12 1107 148 148 158 1 15 16 22 06/12/97 10HFGAL10 209119 Uni-ZAP XR 20 1183 1 1183 179 179 159 1 20 21 96 06/12/9710 HFGAL10 209119 Uni-ZAP XR 135 1766 3 1765 179 179 274 1 17 18 3606/12/97 11 HFKEB72 209119 Uni-ZAP XR 21 1420 1 1420 43 43 160 1 29 3065 06/12/97 12 HFTCU19 209119 Uni-ZAP XR 22 1575 1266 1575 137 137 161 130 31 222 06/12/97 12 HFTCU19 209119 Uni-ZAP XR 136 470 1 470 157 157275 1 24 25 56 06/12/97 13 HFXHN31 209119 Lambda ZAP 23 541 1 541 172172 162 1 30 31 91 06/12/97 II 13 HFXHN31 209119 Lambda ZAP 137 1168 11168 293 293 276 1 22 23 26 06/12/97 II 14 HGLAM53 209119 Uni-ZAP XR 24833 219 833 359 359 163 1 27 28 74 06/12/97 14 HGLAM53 209119 Uni-ZAP XR138 1294 226 1288 369 277 1 26 27 67 06/12/97 15 HJABB94 209119pBluescript 25 1555 1 1555 74 74 164 1 28 29 77 06/12/97 SK- 16 HKIYO61209119 pBluescript 26 1543 1 1543 181 181 165 1 19 20 37 06/12/97 17HLTAI94 209119 Uni-ZAP XR 27 1262 1 1262 47 47 166 1 18 19 44 06/12/9718 HMDAI51 209119 Uni-ZAP XR 28 753 1 753 12 12 167 1 21 22 38 06/12/9719 HMELR03 209119 Lambda ZAP 29 1621 8 1535 200 200 168 1 25 26 17306/12/97 II 20 HMKAH10 209119 pSport1 30 921 1 921 48 48 169 1 43 44 5406/12/97 21 HMKCW19 209119 pSport1 31 2095 473 1934 529 529 170 1 30 31344 06/12/97 21 HMKCW19 209119 pSport1 139 1720 103 1692 188 188 278 127 28 45 06/12/97 22 HMSJW18 209119 Uni-ZAP XR 32 1838 1 1838 28 28 1711 23 24 89 06/12/97 23 HMWGY01 209119 Uni-Zap XR 33 782 1 782 423 423172 1 30 31 104 06/12/97 23 HMWGY01 209119 Uni-Zap XR 140 774 1 774 1717 279 1 31 32 39 06/12/97 24 HNFID82 209119 pBluescript 34 1560 1 1560161 161 173 1 17 18 41 06/12/97 25 HNFIG36 209119 pBluescript 35 1092 11082 171 171 174 1 18 19 46 06/12/97 26 HNGEV29 209119 Uni-ZAP XR 361153 1 1153 173 173 175 1 30 31 73 06/12/97 26 HNGEV29 209119 Uni-ZAP XR141 1566 1 1566 79 79 280 1 10 06/12/97 27 HNGIK21 209119 Uni-ZAP XR 37985 1 985 152 152 176 1 25 26 28 06/12/97 28 HNGJJ65 209124 Uni-ZAP XR38 1122 1 1122 84 84 177 1 22 23 67 06/19/97 29 HNGJU42 209124 Uni-ZAPXR 39 598 6 598 273 273 178 1 17 18 23 06/19/97 30 HODAZ26 209124Uni-ZAP XR 40 1129 8 1129 133 133 179 1 30 06/19/97 31 HODDB05 209124Uni-ZAP XR 41 1158 22 1158 244 244 180 1 10 06/19/97 32 HOFAF39 209124pSport1 42 1767 1 1767 57 57 181 1 22 23 31 06/19/97 33 HOFNY71 209124pCMVSport 43 917 1 917 114 114 182 1 31 32 35 06/19/97 2.0 34 HORBI81209124 Uni-ZAP XR 44 1987 8 1965 31 31 183 1 34 35 34 06/19/97 35HOSCY73 209124 Uni-ZAP XR 45 2053 196 2048 209 209 184 1 28 06/19/97 36HPMBR15 209124 Uni-ZAP XR 46 1272 25 1272 262 262 185 1 5 06/19/97 37HSAVD46 209124 Uni-ZAP XR 47 773 2 767 155 155 186 1 20 21 58 06/19/9738 HSLBF69 209124 Uni-ZAP XR 48 2119 1 2119 107 107 187 1 19 20 40506/19/97 39 HSOAH66 209124 Uni-ZAP XR 49 1188 7 1188 196 196 188 1 27 2836 06/19/97 39 HSOAH66 209124 Uni-ZAP XR 143 537 1 537 136 136 282 1 2122 47 06/19/97 40 HSVBH58 209124 Uni-ZAP XR 50 478 24 155 249 249 189 140 41 57 06/19/97 40 HSVBH58 209124 Uni-ZAP XR 144 680 1 680 168 168 2831 20 21 22 06/19/97 41 HSZAF47 209124 Uni-ZAP XR 51 1333 2 1333 107 107190 1 18 19 126 06/19/97 42 HTADV27 209124 Uni-ZAP XR 52 1255 14 1255 6969 191 1 20 21 20 06/19/97 43 HTADX17 209124 Uni-ZAP XR 53 1140 22 114084 84 192 1 24 25 142 06/19/97 44 HTDAD22 209124 pSport1 54 1220 1 1220193 193 193 1 37 38 109 06/19/97 45 HTEDS39 209124 Uni-ZAP XR 55 694 198694 205 205 194 1 21 22 80 06/19/97 45 HTEDS39 209124 Uni-ZAP XR 1451048 1 1048 227 284 1 20 06/19/97 46 HTEHH53 209124 Uni-ZAP XR 56 988 1980 22 22 195 1 24 25 209 06/19/97 47 HTLDP69 209124 Uni-ZAP XR 57 1500237 1500 330 330 196 1 29 30 148 06/19/97 48 HTNBR95 209124 pBluescript58 1391 1 1386 70 70 197 1 28 29 35 06/19/97 SK- 49 HTPCS60 209124Uni-ZAP XR 59 1579 7 1259 105 105 198 1 19 20 257 06/19/97 50 HUKBH05209124 Lambda ZAP 60 1241 1 1215 151 151 199 1 18 19 58 06/19/97 II 51HUKEX85 209124 Lambda ZAP 61 930 7 925 35 35 200 1 18 19 33 06/19/97 II51 HUKEX85 209124 Lambda ZAP 146 930 6 917 83 83 285 1 30 31 12206/19/97 II 52 HWTBM45 209124 Uni-ZAP XR 62 998 1 998 69 69 201 1 19 2025 06/19/97 53 HADFF38 209124 pSport1 63 1193 1 1034 64 64 202 1 19 2033 06/19/97 54 HADFK68 209124 pSport1 64 830 1 830 91 91 203 1 24 25 5806/19/97 54 HADFK68 209124 pSport1 147 830 1 830 45 45 286 1 26 27 2606/19/97 55 HADGG19 209125 pSport1 65 867 1 867 262 262 204 1 30 31 7506/19/97 55 HADGG19 209125 pSport1 148 865 1 865 281 281 287 1 706/19/97 56 HAEAV45 209125 pBluescript 66 685 46 647 487 487 205 1 34 3566 06/19/97 SK- 56 HAEAV45 209125 pBluescript 149 545 1 545 24 24 288 125 26 28 06/19/97 SK- 57 HARAA15 209125 pBluescript 67 801 1 801 185 185206 1 34 35 43 06/19/97 SK- 58 HATDL27 209125 Uni-ZAP XR 68 908 1 908 8282 207 1 28 29 31 06/19/97 59 HBAFQ54 209125 pSport1 69 696 209 696 229229 208 1 20 21 47 06/19/97 60 HBGBAI4 209125 Uni-ZAP XR 70 455 1 452 3232 209 1 24 25 36 06/19/97 61 HBIAS26 209125 Uni-ZAP XR 71 413 1 372 5757 210 1 27 28 73 06/19/97 62 HBJFU48 209125 Uni-ZAP XR 72 849 1 849 2020 211 1 39 40 40 06/19/97 63 HBJFV28 209125 Uni-ZAP XR 73 505 1 505 306306 212 1 21 22 53 06/19/97 64 HBMWB01 209125 Uni-ZAP XR 74 719 1 719 4848 213 1 17 18 62 06/19/97 65 HBMXN79 209125 Uni-ZAP XR 75 1274 141 974192 192 214 1 44 45 175 06/19/97 66 HBMXP84 209125 Uni-ZAP XR 76 519 1519 161 161 215 1 31 32 39 06/19/97 67 HCFMM26 209125 pSport1 77 389 1389 178 178 216 1 27 28 54 06/19/97 68 HCNAV36 209125 Lambda ZAP 78 823411 823 505 505 217 1 15 16 46 06/19/97 II 69 HCNSB01 209125 pBluescript79 2455 533 1308 552 552 218 1 22 23 179 06/19/97 70 HCRBR74 209125Uni-ZAP XR 80 921 365 911 415 415 219 1 20 21 98 06/19/97 71 HCUBN59209125 ZAP Express 81 678 1 678 96 96 220 1 39 40 43 06/19/97 72 HCUDB38209125 ZAP Express 82 857 1 857 221 221 221 1 17 18 41 06/19/97 73HCUFZ62 209125 ZAP Express 83 1977 28 661 233 233 222 1 28 29 5106/19/97 74 HDHMB42 209125 pCMVSport 84 1149 427 1149 592 592 223 1 2627 31 06/19/97 2.0 75 HDPCO25 209125 pCMVSport 85 767 76 767 182 182 2241 20 21 53 06/19/97 3.0 76 HDPHI51 209125 pCMVSport 86 728 1 728 245 245225 1 30 31 40 06/19/97 3.0 77 HE2EC79 209125 Uni-ZAP XR 87 735 1 735151 151 226 1 21 22 30 06/19/97 78 HE9FE83 209125 Uni-ZAP XR 88 889 332889 351 351 227 1 21 22 59 06/19/97 79 HE9HW52 209125 Uni-ZAP XR 89 56973 569 122 122 228 1 25 26 34 06/19/97 80 HEBFL88 209125 Uni-ZAP XR 90334 2 334 76 76 229 1 22 23 38 06/19/97 81 HFIVB57 209125 pSport1 91 79592 795 286 286 230 1 35 36 38 06/19/97 82 HFPDE69 209125 Uni-ZAP XR 92577 1 577 72 72 231 1 33 34 61 06/19/97 83 HGBGV89 209125 Uni-ZAP XR 93968 1 968 55 55 232 1 26 27 197 06/19/97 84 HGLDE38 209125 Uni-ZAP XR 94553 1 553 31 31 233 1 19 20 61 06/19/97 85 HHGDU58 209125 Lambda ZAP 95968 70 898 235 235 234 1 46 47 80 06/19/97 II 86 HHTLF25 209125 ZAPExpress 96 697 1 661 142 142 235 1 26 27 111 06/19/97 87 HJMAV91 209125pCMVSport 97 866 74 866 251 251 236 1 16 17 32 06/19/97 3.0 88 HKAFB88209125 pCMVSport 98 1368 219 795 238 238 237 1 45 46 228 06/19/97 2.0 89HLHFP03 209126 Uni-ZAP XR 99 613 1 613 224 224 238 1 20 21 116 06/19/9790 HLNAB07 209126 Lambda ZAP 100 685 1 685 187 187 239 1 32 33 3606/19/97 II 91 HLWCF05 209126 pCMVSport 101 646 1 646 155 155 240 1 3637 58 06/19/97 3.0 92 HLYAF80 209126 pSport1 102 826 1 826 222 222 241 124 25 47 06/19/97 93 HMDAA66 209126 Uni-ZAP XR 103 586 1 586 106 106 2421 23 24 31 06/19/97 94 HMKDD07 209126 pSport1 104 628 43 628 267 267 2431 29 30 63 06/19/97 95 HMKDS08 209126 pSport1 105 558 1 558 230 230 2441 30 31 67 06/19/97 96 HMSHM14 209126 Uni-ZAP XR 106 756 1 756 103 103245 1 29 30 45 06/19/97 97 HMWDC28 209126 Uni-Zap XR 107 1146 105 754124 124 246 1 30 31 42 06/19/97 98 HNDAH54 209126 pCMVSport 108 775 1775 26 26 247 1 20 21 31 06/19/97 2.0 99 HNFDS53 209126 Uni-ZAP XR 109911 1 911 200 200 248 1 22 23 23 06/19/97 100 HNFIU96 209126 pBluescript110 456 1 456 170 170 249 1 33 34 79 06/19/97 101 HNGAC63 209126 Uni-ZAPXR 111 554 1 554 214 214 250 1 15 06/19/97 102 HNGAX58 209126 Uni-ZAP XR112 722 1 722 100 100 251 1 16 17 46 06/19/97 103 HNGEM24 209126 Uni-ZAPXR 113 931 1 931 239 239 252 1 30 31 31 06/19/97 104 HNGPT78 209126Uni-ZAP XR 114 588 1 588 20 20 253 1 29 30 35 06/19/97 105 HNHDL85209126 Uni-ZAP XR 115 812 1 812 194 194 254 1 22 23 50 06/19/97 106HNHFU59 209126 Uni-ZAP XR 116 506 1 506 278 278 255 1 16 17 76 06/19/97107 HNHFW22 209126 Uni-ZAP XR 117 751 1 751 228 228 256 1 26 27 6006/19/97 108 HOAAF80 209126 Uni-ZAP XR 118 960 131 960 303 303 257 1 3334 36 06/19/97 109 HODCJ90 209126 Uni-ZAP XR 119 1442 326 1133 344 344258 1 18 19 42 06/19/97 110 HOECO90 209126 Uni-ZAP XR 120 845 215 845299 299 259 1 24 25 38 06/19/97 111 HPEBT80 209126 Uni-ZAP XR 121 360 1360 21 21 260 1 40 41 50 06/19/97 112 HSDAG05 209126 Uni-ZAP XR 122 944231 848 419 419 261 1 37 38 75 06/19/97 113 HSDGR57 209126 Uni-ZAP XR123 914 115 914 195 195 262 1 21 22 44 06/19/97 114 HSDJJ82 209126Uni-ZAP XR 124 462 1 462 79 79 263 1 32 33 52 06/19/97 115 HSDZM95209126 pBluescript 125 545 1 545 223 223 264 1 23 24 42 06/19/97 116HSIDI15 209126 Uni-ZAP XR 126 912 1 873 273 273 265 1 22 23 74 06/19/97117 HSKYU29 209126 pBluescript 127 1048 1 1047 290 290 266 1 36 37 5106/19/97 118 HSNAA55 209126 Uni-ZAP XR 128 722 1 722 35 35 267 1 15 1640 06/19/97 119 HSQFP66 209126 Uni-ZAP XR 129 477 1 477 96 96 268 1 3233 78 06/19/97 120 HSRDE35 209126 Uni-ZAP XR 130 1296 232 804 428 428269 1 21 22 116 06/19/97 121 HSSJN64 209126 Uni-ZAP XR 131 738 1 738 7070 270 1 33 34 61 06/19/97 122 HSVAQ28 209126 Uni-ZAP XR 132 442 1 442149 149 271 1 24 25 98 06/19/97 123 HSVAY16 209126 Uni-ZAP XR 133 882 1790 52 52 272 1 30 31 31 06/19/97

[0843] Table 1 summarizes the information corresponding to each “GeneNo.” described above. The nucleotide sequence identified as “NT SEQ IDNO:X” was assembled from partially homologous (“overlapping”) sequencesobtained from the “cDNA clone ID” identified in Table 1 and, in somecases, from additional related DNA clones. The overlapping sequenceswere assembled into a single contiguous sequence of high redundancy(usually three to five overlapping sequences at each nucleotideposition), resulting in a final sequence identified as SEQ ID NO:X.

[0844] The cDNA Clone ID was deposited on the date and given thecorresponding deposit number listed in “ATCC Deposit No:Z and Date.”Some of the deposits contain multiple different clones corresponding tothe same gene. “Vector” refers to the type of vector contained in thecDNA Clone ID.

[0845] “Total NT Seq.” refers to the total number of nucleotides in thecontig identified by “Gene No.” The deposited clone may contain all ormost of these sequences, reflected by the nucleotide position indicatedas “5′ NT of Clone Seq.” and the “3′ NT of Clone Seq.” of SEQ ID NO:X.The nucleotide position of SEQ ID NO:X of the putative start codon(methionine) is identified as “5′ NT of Start Codon.” Similarly, thenucleotide position of SEQ ID NO:X of the predicted signal sequence isidentified as “5′ NT of First AA of Signal Pep.”

[0846] The translated amino acid sequence, beginning with themethionine, is identified as “AA SEQ ID NO:Y,” although other readingframes can also be easily translated using known molecular biologytechniques. The polypeptides produced by these alternative open readingframes are specifically contemplated by the present invention.

[0847] The first and last amino acid position of SEQ ID NO:Y of thepredicted signal peptide is identified as “First AA of Sig Pep” and“Last AA of Sig Pep.” The predicted first amino acid position of SEQ IDNO:Y of the secreted portion is identified as “Predicted First AA ofSecreted Portion.” Finally, the amino acid position of SEQ ID NO:Y ofthe last amino acid in the open reading frame is identified as “Last AAof ORF.”

[0848] SEQ ID NO:X and the translated SEQ ID NO:Y are sufficientlyaccurate and otherwise suitable for a variety of uses well known in theart and described further below. For instance, SEQ ID NO:X is useful fordesigning nucleic acid hybridization probes that will detect nucleicacid sequences contained in SEQ ID NO:X or the cDNA contained in thedeposited clone. These probes will also hybridize to nucleic acidmolecules in biological samples, thereby enabling a variety of forensicand diagnostic methods of the invention. Similarly, polypeptidesidentified from SEQ ID NO:Y may be used to generate antibodies whichbind specifically to the secreted proteins encoded by the cDNA clonesidentified in Table 1.

[0849] Nevertheless, DNA sequences generated by sequencing reactions cancontain sequencing errors. The errors exist as misidentifiednucleotides, or as insertions or deletions of nucleotides in thegenerated DNA sequence. The erroneously inserted or deleted nucleotidescause frame shifts in the reading frames of the predicted amino acidsequence. In these cases, the predicted amino acid sequence divergesfrom the actual amino acid sequence, even though the generated DNAsequence may be greater than 99.9% identical to the actual DNA sequence(for example, one base insertion or deletion in an open reading frame ofover 1000 bases).

[0850] Accordingly, for those applications requiring precision in thenucleotide sequence or the amino acid sequence, the present inventionprovides not only the generated nucleotide sequence identified as SEQ IDNO:X and the predicted translated amino acid sequence identified as SEQID NO:Y, but also a sample of plasmid DNA containing a human cDNA of theinvention deposited with the ATCC, as set forth in Table 1. Thenucleotide sequence of each deposited clone can readily be determined bysequencing the deposited clone in accordance with known methods. Thepredicted amino acid sequence can then be verified from such deposits.Moreover, the amino acid sequence of the protein encoded by a particularclone can also be directly determined by peptide sequencing or byexpressing the protein in a suitable host cell containing the depositedhuman cDNA, collecting the protein, and determining its sequence.

[0851] The present invention also relates to the genes corresponding toSEQ ID NO:X, SEQ ID NO:Y, or the deposited clone. The corresponding genecan be isolated in accordance with known methods using the sequenceinformation disclosed herein. Such methods include preparing probes orprimers from the disclosed sequence and identifying or amplifying thecorresponding gene from appropriate sources of genomic material.

[0852] Also provided in the present invention are species homologs.Species homologs may be isolated and identified by making suitableprobes or primers from the sequences provided herein and screening asuitable nucleic acid source for the desired homologue.

[0853] The polypeptides of the invention can be prepared in any suitablemanner. Such polypeptides include isolated naturally occurringpolypeptides, recombinantly produced polypeptides, syntheticallyproduced polypeptides, or polypeptides produced by a combination ofthese methods. Means for preparing such polypeptides are well understoodin the art.

[0854] The polypeptides may be in the form of the secreted protein,including the mature form. or may be a part of a larger protein, such asa fusion protein (see below). It is often advantageous to include anadditional amino acid sequence which contains secretory or leadersequences, pro-sequences, sequences which aid in purification, such asmultiple histidine residues, or an additional sequence for stabilityduring recombinant production.

[0855] The polypeptides of the present invention are preferably providedin an isolated form, and preferably are substantially purified. Arecombinantly produced version of a polypeptide, including the secretedpolypeptide, can be substantially purified by the one-step methoddescribed in Smith and Johnson, Gene 67:31-40 (1988). Polypeptides ofthe invention also can be purified from natural or recombinant sourcesusing antibodies of the invention raised against the secreted protein inmethods which are well known in the art.

[0856] Signal Sequences

[0857] Methods for predicting whether a protein has a signal sequence,as well as the cleavage point for that sequence, are available. Forinstance, the method of McGeoch, Virus Res. 3:271-286 (1985), uses theinformation from a short N-terminal charged region and a subsequentuncharged region of the complete (uncleaved) protein. The method of vonHeinje, Nucleic Acids Res. 14:4683-4690 (1986) uses the information fromthe residues surrounding the cleavage site, typically residues −13 to+2, where +1 indicates the amino terminus of the secreted protein. Theaccuracy of predicting the cleavage points of known mammalian secretoryproteins for each of these methods is in the range of 75-80%. (vonHeinje, supra.) However, the two methods do not always produce the samepredicted cleavage point(s) for a given protein.

[0858] In the present case, the deduced amino acid sequence of thesecreted polypeptide was analyzed by a computer program called SignalP(Henrik Nielsen et al., Protein Engineering 10: 1-6 (1997)), whichpredicts the cellular location of a protein based on the amino acidsequence. As part of this computational prediction of localization, themethods of McGeoch and von Heinje are incorporated. The analysis of theamino acid sequences of the secreted proteins described herein by thisprogram provided the results shown in Table 1.

[0859] As one of ordinary skill would appreciate, however, cleavagesites sometimes vary from organism to organism and cannot be predictedwith absolute certainty. Accordingly, the present invention providessecreted polypeptides having a sequence shown in SEQ ID NO:Y which havean N-terminus beginning within 5 residues (i.e., +or −5 residues) of thepredicted cleavage point. Similarly, it is also recognized that in somecases, cleavage of the signal sequence from a secreted protein is notentirely uniform, resulting in more than one secreted species. Thesepolypeptides, and the polynucleotides encoding such polypeptides, arecontemplated by the present invention.

[0860] Moreover, the signal sequence identified by the above analysismay not necessarily predict the naturally occurring signal sequence. Forexample, the naturally occurring signal sequence may be further upstreamfrom the predicted signal sequence. However, it is likely that thepredicted signal sequence will be capable of directing the secretedprotein to the ER. These polypeptides, and the polynucleotides encodingsuch polypeptides, are contemplated by the present invention.

[0861] Polynucleotide and Polypeptide Variants

[0862] “Variant” refers to a polynucleotide or polypeptide differingfrom the polynucleotide or polypeptide of the present invention, butretaining essential properties thereof. Generally, variants are overallclosely similar, and, in many regions, identical to the polynucleotideor polypeptide of the present invention.

[0863] By a polynucleotide having a nucleotide sequence at least, forexample, 95% “identical” to a reference nucleotide sequence of thepresent invention, it is intended that the nucleotide sequence of thepolynucleotide is identical to the reference sequence except that thepolynucleotide sequence may include up to five point mutations per each100 nucleotides of the reference nucleotide sequence encoding thepolypeptide. In other words, to obtain a polynucleotide having anucleotide sequence at least 95% identical to a reference nucleotidesequence, up to 5% of the nucleotides in the reference sequence may bedeleted or substituted with another nucleotide, or a number ofnucleotides up to 5% of the total nucleotides in the reference sequencemay be inserted into the reference sequence. The query sequence may bean entire sequence shown in Table 1, the ORF (open reading frame), orany fragement specified as described herein.

[0864] As a practical matter, whether any particular nucleic acidmolecule or polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99%identical to a nucleotide sequence of the presence invention can bedetermined conventionally using known computer programs. A preferredmethod for determing the best overall match between a query sequence (asequence of the present invention) and a subject sequence, also referredto as a global sequence alignment, can be determined using the FASTDBcomputer program based on the algorithm of Brutlag et al. (Comp. App.Biosci. (1990) 6:237-245). In a sequence alignment the query and subjectsequences are both DNA sequences. An RNA sequence can be compared byconverting U's to T's. The result of said global sequence alignment isin percent identity. Preferred parameters used in a FASTDB alignment ofDNA sequences to calculate percent identiy are: Matrix=Unitary.k-tuple=4, Mismatch Penalty=1, Joining Penalty=30, Randomization GroupLength=0, Cutoff Score=1, Gap Penalty=5, Gap Size Penalty 0.05, WindowSize=500 or the lenght of the subject nucleotide sequence, whichever isshorter.

[0865] If the subject sequence is shorter than the query sequencebecause of 5′ or 3′ deletions, not because of internal deletions, amanual correction must be made to the results. This is because theFASTDB program does not account for 5′ and 3′ truncations of the subjectsequence when calculating percent identity. For subject sequencestruncated at the 5′ or 3′ ends, relative to the the query sequence, thepercent identity is corrected by calculating the number of bases of thequery sequence that are 5′ and 3′ of the subject sequence, which are notmatched/aligned, as a percent of the total bases of the query sequence.Whether a nucleotide is matched/aligned is determined by results of theFASTDB sequence alignment. This percentage is then subtracted from thepercent identity, calculated by the above FASTDB program using thespecified parameters, to arrive at a final percent identity score. Thiscorrected score is what is used for the purposes of the presentinvention. Only bases outside the 5′ and 3′ bases of the subjectsequence, as displayed by the FASTDB alignment, which are notmatched/aligned with the query sequence, are calculated for the purposesof manually adjusting the percent identity score.

[0866] For example, a 90 base subject sequence is aligned to a 100 basequery sequence to determine percent identity. The deletions occur at the5′ end of the subject sequence and therefore, the FASTDB alignment doesnot show a matched/alignement of the first 10 bases at 5′ end. The 10unpaired bases represent 10% of the sequence (number of bases at the 5′and 3′ ends not matched/total number of bases in the query sequence) so10% is subtracted from the percent identity score calculated by theFASTDB program. If the remaining 90 bases were perfectly matched thefinal percent identity would be 90%. In another example, a 90 basesubject sequence is compared with a 100 base query sequence. This timethe deletions are internal deletions so that there are no bases on the5′ or 3′ of the subject sequence which are not matched/aligned with thequery. In this case the percent identity calculated by FASTDB is notmanually corrected. Once again, only bases 5′ and 3′ of the subjectsequence which are not matched/aligned with the query sequnce aremanually corrected for. No other manual corrections are to made for thepurposes of the present invention.

[0867] By a polypeptide having an amino acid sequence at least, forexample, 95% “identical” to a query amino acid sequence of the presentinvention, it is intended that the amino acid sequence of the subjectpolypeptide is identical to the query sequence except that the subjectpolypeptide sequence may include up to five amino acid alterations pereach 100 amino acids of the query amino acid sequence. In other words,to obtain a polypeptide having an amino acid sequence at least 95%identical to a query amino acid sequence, up to 5% of the amino acidresidues in the subject sequence may be inserted, deleted, (indels) orsubstituted with another amino acid. These alterations of the referencesequence may occur at the amino or carboxy terminal positions of thereference amino acid sequence or anywhere between those terminalpositions, interspersed either individually among residues in thereference sequence or in one or more contiguous groups within thereference sequence.

[0868] As a practical matter, whether any particular polypeptide is atleast 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, theamino acid sequences shown in Table 1 or to the amino acid sequenceencoded by deposited DNA clone can be determined conventionally usingknown computer programs. A preferred method for determing the bestoverall match between a query sequence (a sequence of the presentinvention) and a subject sequence, also referred to as a global sequencealignment, can be determined using the FASTDB computer program based onthe algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:237-245).In a sequence alignment the query and subject sequences are either bothnucleotide sequences or both amino acid sequences. The result of saidglobal sequence alignment is in percent identity. Preferred parametersused in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2,Mismatch Penalty=1, Joining Penalty=20, Randomization Group Length=0,Cutoff Score=1, Window Size=sequence length, Gap Penalty=5. Gap SizePenalty=0.05, Window Size=500 or the length of the subject amino acidsequence, whichever is shorter.

[0869] If the subject sequence is shorter than the query sequence due toN- or C-terminal deletions, not because of internal deletions, a manualcorrection must be made to the results. This is becuase the FASTDBprogram does not account for N- and C-terminal truncations of thesubject sequence when calculating global percent identity. For subjectsequences truncated at the N- and C-termini, relative to the the querysequence, the percent identity is corrected by calculating the number ofresidues of the query sequence that are N- and C-terminal of the subjectsequence, which are not matched/aligned with a corresponding subjectresidue, as a percent of the total bases of the query sequence. Whethera residue is matched/aligned is determined by results of the FASTDBsequence alignment. This percentage is then subtracted from the percentidentity, calculated by the above FASTDB program using the specifiedparameters, to arrive at a final percent identity score. This finalpercent identity score is what is used for the purposes of the presentinvention. Only residues to the N- and C-termini of the subjectsequence, which are not matched/aligned with the query sequence, areconsidered for the purposes of manually adjusting the percent identityscore. That is, only query residue positions outside the farthest N- andC-terminal residues of the subject sequence.

[0870] For example, a 90 amino acid residue subject sequence is alignedwith a 100 residue query sequence to determine percent identity. Thedeletion occurs at the N-terminus of the subject sequence and therefore,the FASTDB alignment does not show a matching/alignment of the first 10residues at the N-terminus. The 10 unpaired residues represent 10% ofthe sequence (number of residues at the N- and C-termini notmatched/total number of residues in the query sequence) so 10% issubtracted from the percent identity score calculated by the FASTDBprogram. If the remaining 90 residues were perfectly matched the finalpercent identity would be 90%. In another example, a 90 residue subjectsequence is compared with a 100 residue query sequence. This time thedeletions are internal deletions so there are no residues at the N- orC-termini of the subject sequence which are not matched/aligned with thequery. In this case the percent identity calculated by FASTDB is notmanually corrected. Once again, only residue positions outside the N-and C-terminal ends of the subject sequence, as displayed in the FASTDBalignment, which are not matched/aligned with the query sequnce aremanually corrected for. No other manual corrections are to made for thepurposes of the present invention.

[0871] The variants may contain alterations in the coding regions,non-coding regions, or both. Especially preferred are polynucleotidevariants containing alterations which produce silent substitutions,additions, or deletions, but do not alter the properties or activitiesof the encoded polypeptide. Nucleotide variants produced by silentsubstitutions due to the degeneracy of the genetic code are preferred.Moreover, variants in which 5-10, 1-5, or 1-2 amino acids aresubstituted, deleted, or added in any combination are also preferred.Polynucleotide variants can be produced for a variety of reasons, e.g.,to optimize codon expression for a particular host (change codons in thehuman mRNA to those preferred by a bacterial host such as E. coli).

[0872] Naturally occurring variants are called “allelic variants,” andrefer to one of several alternate forms of a gene occupying a givenlocus on a chromosome of an organism. (Genes II, Lewin, B., ed., JohnWiley & Sons, New York (1985).) These allelic variants can vary ateither the polynucleotide and/or polypeptide level. Alternatively,non-naturally occurring variants may be produced by mutagenesistechniques or by direct synthesis.

[0873] Using known methods of protein engineering and recombinant DNAtechnology, variants may be generated to improve or alter thecharacteristics of the polypeptides of the present invention. Forinstance, one or more amino acids can be deleted from the N-terminus orC-terminus of the secreted protein without substantial loss ofbiological function. The authors of Ron et al., J. Biol. Chem. 268:2984-2988 (1993), reported variant KGF proteins having heparin bindingactivity even after deleting 3, 8, or 27 amino-terminal amino acidresidues. Similarly, Interferon gamma exhibited up to ten times higheractivity after deleting 8-10 amino acid residues from the carboxyterminus of this protein. (Dobeli et al., J. Biotechnology 7:199-216(1988).)

[0874] Moreover, ample evidence demonstrates that variants often retaina biological activity similar to that of the naturally occurringprotein. For example, Gayle and coworkers (J. Biol. Chem 268:22105-22111(1993)) conducted extensive mutational analysis of human cytokine IL-1a.They used random mutagenesis to generate over 3,500 individual IL-1amutants that averaged 2.5 amino acid changes per variant over the entirelength of the molecule. Multiple mutations were examined at everypossible amino acid position. The investigators found that “[m]ost ofthe molecule could be altered with little effect on either [binding orbiological activity].” (See, Abstract.) In fact, only 23 unique aminoacid sequences, out of more than 3,500 nucleotide sequences examined,produced a protein that significantly differed in activity fromwild-type.

[0875] Furthermore, even if deleting one or more amino acids from theN-terminus or C-terminus of a polypeptide results in modification orloss of one or more biological functions, other biological activitiesmay still be retained. For example, the ability of a deletion variant toinduce and/or to bind antibodies which recognize the secreted form willlikely be retained when less than the majority of the residues of thesecreted form are removed from the N-terminus or C-terminus. Whether aparticular polypeptide lacking N- or C-terminal residues of a proteinretains such immunogenic activities can readily be determined by routinemethods described herein and otherwise known in the art.

[0876] Thus, the invention further includes polypeptide variants whichshow substantial biological activity. Such variants include deletions,insertions, inversions, repeats, and substitutions selected according togeneral rules known in the art so as have little effect on activity. Forexample, guidance concerning how to make phenotypically silent aminoacid substitutions is provided in Bowie, J. U. et al., Science247:1306-1310 (1990), wherein the authors indicate that there are twomain strategies for studying the tolerance of an amino acid sequence tochange.

[0877] The first strategy exploits the tolerance of amino acidsubstitutions by natural selection during the process of evolution. Bycomparing amino acid sequences in different species, conserved aminoacids can be identified. These conserved amino acids are likelyimportant for protein function. In contrast, the amino acid positionswhere substitutions have been tolerated by natural selection indicatesthat these positions are not critical for protein function. Thus,positions tolerating amino acid substitution could be modified whilestill maintaining biological activity of the protein.

[0878] The second strategy uses genetic engineering to introduce aminoacid changes at specific positions of a cloned gene to identify regionscritical for protein function. For example, site directed mutagenesis oralanine-scanning mutagenesis (introduction of single alanine mutationsat every residue in the molecule) can be used. (Cunningham and Wells,Science 244:1081-1085 (1989).) The resulting mutant molecules can thenbe tested for biological activity.

[0879] As the authors state, these two strategies have revealed thatproteins are surprisingly tolerant of amino acid substitutions. Theauthors further indicate which amino acid changes are likely to bepermissive at certain amino acid positions in the protein. For example,most buried (within the tertiary structure of the protein) amino acidresidues require nonpolar side chains, whereas few features of surfaceside chains are generally conserved. Moreover, tolerated conservativeamino acid substitutions involve replacement of the aliphatic orhydrophobic amino acids Ala, Val, Leu and Ile; replacement of thehydroxyl residues Ser and Thr; replacement of the acidic residues Aspand Glu; replacement of the amide residues Asn and Gln, replacement ofthe basic residues Lys, Arg, and His; replacement of the aromaticresidues Phe, Tyr, and Trp, and replacement of the small-sized aminoacids Ala, Ser, Thr, Met, and Gly.

[0880] Besides conservative amino acid substitution, variants of thepresent invention include (i) substitutions with one or more of thenon-conserved amino acid residues, where the substituted amino acidresidues may or may not be one encoded by the genetic code, or (ii)substitution with one or more of amino acid residues having asubstituent group, or (iii) fusion of the mature polypeptide withanother compound, such as a compound to increase the stability and/orsolubility of the polypeptide (for example, polyethylene glycol), or(iv) fusion of the polypeptide with additional amino acids, such as anIgG Fc fusion region peptide, or leader or secretory sequence, or asequence facilitating purification. Such variant polypeptides are deemedto be within the scope of those skilled in the art from the teachingsherein.

[0881] For example, polypeptide variants containing amino acidsubstitutions of charged amino acids with other charged or neutral aminoacids may produce proteins with improved characteristics, such as lessaggregation. Aggregation of pharmaceutical formulations both reducesactivity and increases clearance due to the aggregate's immunogenicactivity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967);Robbins et al., Diabetes 36: 838-845 (1987); Cleland et al., Crit. Rev.Therapeutic Drug Carrier Systems 10:307-377 (1993).)

[0882] Polynucleotide and Polypeptide Fragments

[0883] In the present invention, a “polynucleotide fragment” refers to ashort polynucleotide having a nucleic acid sequence contained in thedeposited clone or shown in SEQ ID NO:X. The short nucleotide fragmentsare preferably at least about 15 nt, and more preferably at least about20 nt, still more preferably at least about 30 nt, and even morepreferably, at least about 40 nt in length. A fragment “at least 20 ntin length,” for example, is intended to include 20 or more contiguousbases from the cDNA sequence contained in the deposited clone or thenucleotide sequence shown in SEQ ID NO:X. These nucleotide fragments areuseful as diagnostic probes and primers as discussed herein. Of course,larger fragments (e.g., 50, 150, 500, 600, 2000 nucleotides) arepreferred.

[0884] Moreover, representative examples of polynucleotide fragments ofthe invention, include, for example, fragments having a sequence fromabout nucleotide number 1-50, 51-100, 101-150, 151-200, 201-250,251-300, 301-350, 351-400, 401-450, 451-500, 501-550, 551-600, 651-700,701-750, 751-800, 800-850, 851-900, 901-950, 951-1000, 1001-1050,1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350,1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650,1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950,1951-2000, or 2001 to the end of SEQ ID NO:X or the cDNA contained inthe deposited clone. In this context “about” includes the particularlyrecited ranges, larger or smaller by several (5, 4, 3, 2, or 1)nucleotides, at either terminus or at both termini. Preferably, thesefragments encode a polypeptide which has biological activity. Morepreferably, these polynucleotides can be used as probes or primers asdiscussed herein.

[0885] In the present invention, a “polypeptide fragment” refers to ashort amino acid sequence contained in SEQ ID NO:Y or encoded by thecDNA contained in the deposited clone. Protein fragments may be“free-standing,” or comprised within a larger polypeptide of which thefragment forms a part or region, most preferably as a single continuousregion. Representative examples of polypeptide fragments of theinvention, include, for example, fragments from about amino acid number1-20, 21-40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, or 161 tothe end of the coding region. Moreover, polypeptide fragments can beabout 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150amino acids in length. In this context “about” includes the particularlyrecited ranges, larger or smaller by several (5, 4, 3, 2, or 1) aminoacids, at either extreme or at both extremes.

[0886] Preferred polypeptide fragments include the secreted protein aswell as the mature form. Further preferred polypeptide fragments includethe secreted protein or the mature form having a continuous series ofdeleted residues from the amino or the carboxy terminus, or both. Forexample, any number of amino acids, ranging from 1-60, can be deletedfrom the amino terminus of either the secreted polypeptide or the matureform. Similarly, any number of amino acids, ranging from 1-30, can bedeleted from the carboxy terminus of the secreted protein or matureform. Furthermore, any combination of the above amino and carboxyterminus deletions are preferred. Similarly, polynucleotide fragmentsencoding these polypeptide fragments are also preferred.

[0887] Also preferred are polypeptide and polynucleotide fragmentscharacterized by structural or functional domains, such as fragmentsthat comprise alpha-helix and alpha-helix forming regions, beta-sheetand beta-sheet-forming regions, turn and turn-forming regions, coil andcoil-forming regions, hydrophilic regions, hydrophobic regions, alphaamphipathic regions, beta amphipathic regions, flexible regions,surface-forming regions, substrate binding region, and high antigenicindex regions. Polypeptide fragments of SEQ ID NO:Y falling withinconserved domains are specifically contemplated by the presentinvention. Moreover, polynucleotide fragments encoding these domains arealso contemplated.

[0888] Other preferred fragments are biologically active fragments.Biologically active fragments are those exhibiting activity similar, butnot necessarily identical, to an activity of the polypeptide of thepresent invention. The biological activity of the fragments may includean improved desired activity, or a decreased undesirable activity.

[0889] Epitopes & Antibodies

[0890] In the present invention, “epitopes” refer to polypeptidefragments having antigenic or immunogenic activity in an animal,especially in a human. A preferred embodiment of the present inventionrelates to a polypeptide fragment comprising an epitope, as well as thepolynucleotide encoding this fragment. A region of a protein molecule towhich an antibody can bind is defined as an “antigenic epitope.” Incontrast, an “immunogenic epitope” is defined as a part of a proteinthat elicits an antibody response. (See, for instance, Geysen et al.,Proc. Natl. Acad. Sci. USA 81:3998-4002 (1983).)

[0891] Fragments which function as epitopes may be produced by anyconventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci.USA 82:5131-5135 (1985) further described in U.S. Patent No. 4,631,211.)

[0892] In the present invention, antigenic epitopes preferably contain asequence of at least seven, more preferably at least nine, and mostpreferably between about 15 to about 30 amino acids. Antigenic epitopesare useful to raise antibodies, including monoclonal antibodies, thatspecifically bind the epitope. (See, for instance, Wilson et al., Cell37:767-778 (1984); Sutcliffe, J. G. et al., Science 219:660-666 (1983).)

[0893] Similarly, immunogenic epitopes can be used to induce antibodiesaccording to methods well known in the art. (See, for instance,Sutcliffe et al., supra; Wilson et al., supra; Chow, M. et al., Proc.Natl. Acad. Sci. USA 82:910-914; and Bittle, F. J. et al., J. Gen.Virol. 66:2347-2354 (1985).) A preferred immunogenic epitope includesthe secreted protein. The immunogenic epitopes may be presented togetherwith a carrier protein, such as an albumin, to an animal system (such asrabbit or mouse) or, if it is long enough (at least about 25 aminoacids), without a carrier. However, immunogenic epitopes comprising asfew as 8 to 10 amino acids have been shown to be sufficient to raiseantibodies capable of binding to, at the very least, linear epitopes ina denatured polypeptide (e.g., in Western blotting.)

[0894] As used herein, the term “antibody” (Ab) or “monoclonal antibody”(Mab) is meant to include intact molecules as well as antibody fragments(such as, for example, Fab and F(ab′)2 fragments) which are capable ofspecifically binding to protein. Fab and F(ab′)2 fragments lack the Fcfragment of intact antibody, clear more rapidly from the circulation,and may have less non-specific tissue binding than an intact antibody.(Wahl et al., J. Nucl. Med. 24:316-325 (1983).) Thus, these fragmentsare preferred, as well as the products of a FAB or other immunoglobulinexpression library. Moreover, antibodies of the present inventioninclude chimeric, single chain, and humanized antibodies.

[0895] Fusion Proteins

[0896] Any polypeptide of the present invention can be used to generatefusion proteins. For example, the polypeptide of the present invention,when fused to a second protein, can be used as an antigenic tag.Antibodies raised against the polypeptide of the present invention canbe used to indirectly detect the second protein by binding to thepolypeptide. Moreover, because secreted proteins target cellularlocations based on trafficking signals, the polypeptides of the presentinvention can be used as targeting molecules once fused to otherproteins.

[0897] Examples of domains that can be fused to polypeptides of thepresent invention include not only heterologous signal sequences, butalso other heterologous functional regions. The fusion does notnecessarily need to be direct, but may occur through linker sequences.

[0898] Moreover, fusion proteins may also be engineered to improvecharacteristics of the polypeptide of the present invention. Forinstance, a region of additional amino acids, particularly charged aminoacids, may be added to the N-terminus of the polypeptide to improvestability and persistence during purification from the host cell orsubsequent handling and storage. Also, peptide moieties may be added tothe polypeptfde to facilitate purification. Such regions may be removedprior to final preparation of the polypeptide. The addition of peptidemoieties to facilitate handling of polypeptides are familiar and routinetechniques in the art.

[0899] Moreover, polypeptides of the present invention, includingfragments, and specifically epitopes, can be combined with parts of theconstant domain of immunoglobulins (IgG), resulting in chimericpolypeptides. These fusion proteins facilitate purification and show anincreased half-life in vivo. One reported example describes chimericproteins consisting of the first two domains of the humanCD4-polypeptide and various domains of the constant regions of the heavyor light chains of mammalian immunoglobulins. (EP A 394,827; Trauneckeret al., Nature 331:84-86 (1988).) Fusion proteins havingdisulfide-linked dimeric structures (due to the IgG) can also be moreefficient in binding and neutralizing other molecules, than themonomeric secreted protein or protein fragment alone. (Fountoulakis etal., J. Biochem. 270:3958-3964 (1995).)

[0900] Similarly, EP-A-O 464 533 (Canadian counterpart 2045869)discloses fusion proteins comprising various portions of constant regionof immunoglobulin molecules together with another human protein or partthereof. In many cases, the Fc part in a fusion protein is beneficial intherapy and diagnosis, and thus can result in, for example, improvedpharmacokinetic properties. (EP-A 0232 262.) Alternatively, deleting theFc part after the fusion protein has been expressed, detected, andpurified, would be desired. For example, the Fc portion may hindertherapy and diagnosis if the fusion protein is used as an antigen forimmunizations. In drug discovery, for example, human proteins, such ashIL-5, have been fused with Fc portions for the purpose ofhigh-throughput screening assays to identify antagonists of hIL-5. (See,D. Bennett et al., J. Molecular Recognition 8:52-58 (1995); K. Johansonet al., J. Biol. Chem. 270:9459-9471 (1995).)

[0901] Moreover, the polypeptides of the present invention can be fusedto marker sequences, such as a peptide which facilitates purification ofthe fused polypeptide. In preferred embodiments, the marker amino acidsequence is a hexa-histidine peptide, such as the tag provided in a pQEvector (QIAGEN, Inc., 9259 Eton Avenue, Chatsworth, Calif., 91311),among others, many of which are commercially available. As described inGentz et al., Proc. Natl. Acad. Sci. USA 86:821-824 (1989), forinstance, hexa-histidine provides for convenient purification of thefusion protein. Another peptide tag useful for purification, the “HA”tag, corresponds to an epitope derived from the influenza hemagglutininprotein. (Wilson et al., Cell 37:767 (1984).)

[0902] Thus, any of these above fusions can be engineered using thepolynucleotides or the polypeptides of the present invention.

[0903] Vectors, Host Cells, and Protein Production

[0904] The present invention also relates to vectors containing thepolynucleotide of the present invention, host cells, and the productionof polypeptides by recombinant techniques. The vector may be, forexample, a phage, plasmid, viral, or retroviral vector. Retroviralvectors may be replication competent or replication defective. In thelatter case, viral propagation generally will occur only incomplementing host cells.

[0905] The polynucleotides may be joined to a vector containing aselectable marker for propagation in a host. Generally, a plasmid vectoris introduced in a precipitate, such as a calcium phosphate precipitate,or in a complex with a charged lipid. If the vector is a virus, it maybe packaged in vitro using an appropriate packaging cell line and thentransduced into host cells.

[0906] The polynucleotide insert should be operatively linked to anappropriate promoter, such as the phage lambda PL promoter, the E. colilac, trp, phoA and tac promoters, the SV40 early and late promoters andpromoters of retroviral LTRs, to name a few. Other suitable promoterswill be known to the skilled artisan. The expression constructs willfurther contain sites for transcription initiation, termination, and, inthe transcribed region, a ribosome binding site for translation. Thecoding portion of the transcripts expressed by the constructs willpreferably include a translation initiating codon at the beginning and atermination codon (UAA, UGA or UAG) appropriately positioned at the endof the polypeptide to be translated.

[0907] As indicated, the expression vectors will preferably include atleast one selectable marker. Such markers include dihydrofolatereductase, G418 or neomycin resistance for eukaryotic cell culture andtetracycline, kanamycin or ampicillin resistance genes for culturing inE. coli and other bacteria. Representative examples of appropriate hostsinclude, but are not limited to, bacterial cells, such as E. coli,Streptomyces and Salmonella typhimurium cells; fungal cells, such asyeast cells; insect cells such as Drosophila S2 and Spodoptera Sf9cells; animal cells such as CHO, COS, 293, and Bowes melanoma cells; andplant cells. Appropriate culture mediums and conditions for theabove-described host cells are known in the art.

[0908] Among vectors preferred for use in bacteria include pQE70, pQE60and pQE-9, available from QIAGEN, Inc.; pBluescript vectors, Phagescriptvectors, pNH8A, pNH16a, pNH18A, pNH46A, available from StratageneCloning Systems, Inc.; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5available from Pharmacia Biotech, Inc. Among preferred eukaryoticvectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available fromStratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia.Other suitable vectors will be readily apparent to the skilled artisan.

[0909] Introduction of the construct into the host cell can be effectedby calcium phosphate transfection, DEAE-dextran mediated transfection,cationic lipid-mediated transfection, electroporation, transduction,infection, or other methods. Such methods are described in many standardlaboratory manuals, such as Davis et al., Basic Methods In MolecularBiology (1986). It is specifically contemplated that the polypeptides ofthe present invention may in fact be expressed by a host cell lacking arecombinant vector.

[0910] A polypeptide of this invention can be recovered and purifiedfrom recombinant cell cultures by well-known methods including ammoniumsulfate or ethanol precipitation, acid extraction, anion or cationexchange chromatography, phosphocellulose chromatography, hydrophobicinteraction chromatography, affinity chromatography, hydroxylapatitechromatography and lectin chromatography. Most preferably, highperformance liquid chromatography (“HPLC”) is employed for purification.

[0911] Polypeptides of the present invention, and preferably thesecreted form, can also be recovered from: products purified fromnatural sources, including bodily fluids, tissues and cells, whetherdirectly isolated or cultured; products of chemical syntheticprocedures; and products produced by recombinant techniques from aprokaryotic or eukaryotic host, including, for example, bacterial,yeast, higher plant, insect, and mammalian cells. Depending upon thehost employed in a recombinant production procedure, the polypeptides ofthe present invention may be glycosylated or may be non-glycosylated. Inaddition, polypeptides of the invention may also include an initialmodified methionine residue, in some cases as a result of host-mediatedprocesses. Thus, it is well known in the art that the N-terminalmethionine encoded by the translation initiation codon generally isremoved with high efficiency from any protein after translation in alleukaryotic cells. While the N-terminal methionine on most proteins alsois efficiently removed in most prokaryotes, for some proteins, thisprokaryotic removal process is inefficient, depending on the nature ofthe amino acid to which the N-terminal methionine is covalently linked.

[0912] Uses of the Polynucleotides

[0913] Each of the polynucleotides identified herein can be used innumerous ways as reagents. The following description should beconsidered exemplary and utilizes known techniques.

[0914] The polynucleotides of the present invention are useful forchromosome identification. There exists an ongoing need to identify newchromosome markers, since few chromosome marking reagents, based onactual sequence data (repeat polymorphisms), are presently available.Each polynucleotide of the present invention can be used as a chromosomemarker.

[0915] Briefly, sequences can be mapped to chromosomes by preparing PCRprimers (preferably 15-25 bp) from the sequences shown in SEQ ID NO:X.Primers can be selected using computer analysis so that primers do notspan more than one predicted exon in the genomic DNA. These primers arethen used for PCR, screening of somatic cell hybrids containingindividual human chromosomes. Only those hybrids containing the humangene corresponding to the SEQ ID NO:X will yield an amplified fragment.

[0916] Similarly, somatic hybrids provide a rapid method of PCR mappingthe polynucleotides to particular chromosomes. Three or more clones canbe assigned per day using a single thermal cycler. Moreover,sublocalization of the polynucleotides can be achieved with panels ofspecific chromosome fragments. Other gene mapping strategies that can beused include in situ hybridization, prescreening with labeledflow-sorted chromosomes, and preselection by hybridization to constructchromosome specific-cDNA libraries.

[0917] Precise chromosomal location of the polynucleotides can also beachieved using fluorescence in situ hybridization (FISH) of a metaphasechromosomal spread. This technique uses polynucleotides as short as 500or 600 bases; however, polynucleotides 2,000-4,000 bp are preferred. Fora review of this technique, see Verma et al., “Human Chromosomes: aManual of Basic Techniques,” Pergamon Press, New York (1988).

[0918] For chromosome mapping, the polynucleotides can be usedindividually (to mark a single chromosome or a single site on thatchromosome) or in panels (for marking multiple sites and/or multiplechromosomes). Preferred polynucleotides correspond to the noncodingregions of the cDNAs because the coding sequences are more likelyconserved within gene families, thus increasing the chance of crosshybridization during chromosomal mapping.

[0919] Once a polynucleotide has been mapped to a precise chromosomallocation, the physical position of the polynucleotide can be used inlinkage analysis. Linkage analysis establishes coinheritance between achromosomal location and presentation of a particular disease. (Diseasemapping data are found, for example, in V. McKusick, MendelianInheritance in Man (available on line through Johns Hopkins UniversityWelch Medical Library).) Assuming 1 megabase mapping resolution and onegene per 20 kb, a cDNA precisely localized to a chromosomal regionassociated with the disease could be one of 50-500 potential causativegenes.

[0920] Thus, once coinheritance is established, differences in thepolynucleotide and the corresponding gene between affected andunaffected individuals can be examined. First, visible structuralalterations in the chromosomes, such as deletions or translocations, areexamined in chromosome spreads or by PCR. If no structural alterationsexist, the presence of point mutations are ascertained. Mutationsobserved in some or all affected individuals, but not in normalindividuals, indicates that the mutation may cause the disease. However,complete sequencing of the polypeptide and the corresponding gene fromseveral normal individuals is required to distinguish the mutation froma polymorphism. If a new polymorphism is identified, this polymorphicpolypeptide can be used for further linkage analysis.

[0921] Furthermore, increased or decreased expression of the gene inaffected individuals as compared to unaffected individuals can beassessed using polynucleotides of the present invention. Any of thesealterations (altered expression, chromosomal rearrangement, or mutation)can be used as a diagnostic or prognostic marker.

[0922] In addition to the foregoing, a polynucleotide can be used tocontrol gene expression through triple helix formation or antisense DNAor RNA. Both methods rely on binding of the polynucleotide to DNA orRNA. For these techniques, preferred polynucleotides are usually 20 to40 bases in length and complementary to either the region of the geneinvolved in transcription (triple helix—see Lee et al., Nucl. Acids Res.6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al.,Science 251:1360 (1991) ) or to the mRNA itself (antisense—Okano, J.Neurochem. 56:560 (1991); Oligodeoxy-nucleotides as Antisense Inhibitorsof Gene Expression, CRC Press, Boca Raton, Fla. (1988).) Triple helixformation optimally results in a shut-off of RNA transcription from DNA,while antisense RNA hybridization blocks translation of an mRNA moleculeinto polypeptide. Both techniques are effective in model systems, andthe information disclosed herein can be used to design antisense ortriple helix polynucleotides in an effort to treat disease.

[0923] Polynucleotides of the present invention are also useful in genetherapy. One goal of gene therapy is to insert a normal gene into anorganism having a defective gene, in an effort to correct the geneticdefect. The polynucleotides disclosed in the present invention offer ameans of targeting such genetic defects in a highly accurate manner.Another goal is to insert a new gene that was not present in the hostgenome, thereby producing a new trait in the host cell.

[0924] The polynucleotides are also useful for identifying individualsfrom minute biological samples. The United States military, for example,is considering the use of restriction fragment length polymorphism(RFLP) for identification of its personnel. In this technique, anindividual's genomic DNA is digested with one or more restrictionenzymes, and probed on a Southern blot to yield unique bands foridentifying personnel. This method does not suffer from the currentlimitations of “Dog Tags” which can be lost, switched, or stolen, makingpositive identification difficult. The polynucleotides of the presentinvention can be used as additional DNA markers for RFLP.

[0925] The polynucleotides of the present invention can also be used asan alternative to RFLP, by determining the actual base-by-base DNAsequence of selected portions of an individual's genome. These sequencescan be used to prepare PCR primers for amplifying and isolating suchselected DNA, which can then be sequenced. Using this technique,individuals can be identified because each individual will have a uniqueset of DNA sequences. Once an unique ID database is established for anindividual, positive identification of that individual, living or dead,can be made from extremely small tissue samples.

[0926] Forensic biology also benefits from using DNA-basedidentification techniques as disclosed herein. DNA sequences taken fromvery small biological samples such as tissues, e.g., hair or skin, orbody fluids, e.g., blood, saliva, semen, etc., can be amplified usingPCR. In one prior art technique, gene sequences amplified frompolymorphic loci, such as DQa class II HLA gene, are used in forensicbiology to identify individuals. (Erlich, H., PCR Technology, Freemanand Co. (1992).) Once these specific polymorphic loci are amplified,they are digested with one or more restriction enzymes, yielding anidentifying set of bands on a Southern blot probed with DNAcorresponding to the DQa class II HLA gene. Similarly, polynucleotidesof the present invention can be used as polymorphic markers for forensicpurposes.

[0927] There is also a need for reagents capable of identifying thesource of a particular tissue. Such need arises, for example, inforensics when presented with tissue of unknown origin. Appropriatereagents can comprise, for example, DNA probes or primers specific toparticular tissue prepared from the sequences of the present invention.Panels of such reagents can identify tissue by species and/or by organtype. In a similar fashion, these reagents can be used to screen tissuecultures for contamination.

[0928] In the very least, the polynucleotides of the present inventioncan be used as molecular weight markers on Southern gels, as diagnosticprobes for the presence of a specific mRNA in a particular cell type, asa probe to “subtract-out” known sequences in the process of discoveringnovel polynucleotides, for selecting and making oligomers for attachmentto a “gene chip” or other support, to raise anti-DNA antibodies usingDNA immunization techniques, and as an antigen to elicit an immuneresponse.

[0929] Uses of the Polypeptides

[0930] Each of the polypeptides identified herein can be used innumerous ways. The following description should be considered exemplaryand utilizes known techniques.

[0931] A polypeptide of the present invention can be used to assayprotein levels in a biological sample using antibody-based techniques.For example, protein expression in tissues can be studied with classicalimmunohistological methods. (Jalkanen, M., et al., J. Cell. Biol.101:976-985 (1985); Jalkanen, M., et al., J. Cell . Biol. 105:3087-3096(1987).) Other antibody-based methods useful for detecting protein geneexpression include immunoassays, such as the enzyme linked immunosorbentassay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assaylabels are known in the art and include enzyme labels, such as, glucoseoxidase, and radioisotopes, such as iodine (1251, 121I), carbon (14C),sulfur (35S), tritium (3H), indium ( 12In), and technetium (99mTc), andfluorescent labels, such as fluorescein and rhodamine, and biotin.

[0932] In addition to assaying secreted protein levels in a biologicalsample, proteins can also be detected in vivo by imaging. Antibodylabels or markers for in vivo imaging of protein include thosedetectable by X-radiography, NMR or ESR. For X-radiography, suitablelabels include radioisotopes such as barium or cesium, which emitdetectable radiation but are not overtly harmful to the subject.Suitable markers for NMR and ESR include those with a detectablecharacteristic spin, such as deuterium, which may be incorporated intothe antibody by labeling of nutrients for the relevant hybridoma.

[0933] A protein-specific antibody or antibody fragment which has beenlabeled with an appropriate detectable imaging moiety, such as aradioisotope (for example, 1311I 112In, 99mTc), a radio-opaquesubstance, or a material detectable by nuclear magnetic resonance, isintroduced (for example, parenterally, subcutaneously, orintraperitoneally) into the mammal. It will be understood in the artthat the size of the subject and the imaging system used will determinethe quantity of imaging moiety needed to produce diagnostic images. Inthe case of a radioisotope moiety, for a human subject, the quantity ofradioactivity injected will normally range from about 5 to 20millicuries of 99mTc. The labeled antibody or antibody fragment willthen preferentially accumulate at the location of cells which containthe specific protein. In vivo tumor imaging is described in S. W.Burchiel et al., “Immunopharmacokinetics of Radiolabeled Antibodies andTheir Fragments.” (Chapter 13 in Tumor Imaging: The RadiochemicalDetection of Cancer, S. W. Burchiel and B. A. Rhodes, eds., MassonPublishing Inc. (1982).)

[0934] Thus, the invention provides a diagnostic method of a disorder,which involves (a) assaying the expression of a polypeptide of thepresent invention in cells or body fluid of an individual; (b) comparingthe level of gene expression with a standard gene expression level,whereby an increase or decrease in the assayed polypeptide geneexpression level compared to the standard expression level is indicativeof a disorder.

[0935] Moreover, polypeptides of the present invention can be used totreat disease. For example, patients can be administered a polypeptideof the present invention in an effort to replace absent or decreasedlevels of the polypeptide (e.g., insulin), to supplement absent ordecreased levels of a different polypeptide (e.g., hemoglobin S forhemoglobin B), to inhibit the activity of a polypeptide (e.g., anoncogene), to activate the activity of a polypeptide (e.g., by bindingto a receptor), to reduce the activity of a membrane bound receptor bycompeting with it for free ligand (e.g., soluble TNF receptors used inreducing inflammation), or to bring about a desired response (e.g.,blood vessel growth).

[0936] Similarly, antibodies directed to a polypeptide of the presentinvention can also be used to treat disease. For example, administrationof an antibody directed to a polypeptide of the present invention canbind and reduce overproduction of the polypeptide. Similarly,administration of an antibody can activate the polypeptide, such as bybinding to a polypeptide bound to a membrane (receptor).

[0937] At the very least, the polypeptides of the present invention canbe used as molecular weight markers on SDS-PAGE gels or on molecularsieve gel filtration columns using methods well known to those of skillin the art. Polypeptides can also be used to raise antibodies, which inturn are used to measure protein expression from a recombinant cell, asa way of assessing transformation of the host cell. Moreover, thepolypeptides of the present invention can be used to test the followingbiological activities.

[0938] Biological Activities

[0939] The polynucleotides and polypeptides of the present invention canbe used in assays to test for one or more biological activities. Ifthese polynucleotides and polypeptides do exhibit activity in aparticular assay, it is likely that these molecules may be involved inthe diseases associated with the biological activity. Thus, thepolynucleotides and polypeptides could be used to treat the associateddisease.

[0940] Immune Activity

[0941] A polypeptide or polynucleotide of the present invention may beuseful in treating deficiencies or disorders of the immune system, byactivating or inhibiting the proliferation, differentiation, ormobilization (chemotaxis) of immune cells. Immune cells develop througha process called hematopoiesis, producing myeloid (platelets, red bloodcells, neutrophils, and macrophages) and lymphoid (B and T lymphocytes)cells from pluripotent stem cells. The etiology of these immunedeficiencies or disorders may be genetic, somatic, such as cancer orsome autoimmune disorders, acquired (e.g., by chemotherapy or toxins),or infectious. Moreover, a polynucleotide or polypeptide of the presentinvention can be used as a marker or detector of a particular immunesystem disease or disorder.

[0942] A polynucleotide or polypeptide of the present invention may beuseful in treating or detecting deficiencies or disorders ofhematopoietic cells. A polypeptide or polynucleotide of the presentinvention could be used to increase differentiation and proliferation ofhematopoietic cells, including the pluripotent stem cells, in an effortto treat those disorders associated with a decrease in certain (or many)types hematopoietic cells. Examples of immunologic deficiency syndromesinclude, but are not limited to: blood protein disorders (e.g.agammaglobulinemia, dysgammaglobulinemia), ataxia telangiectasia, commonvariable immunodeficiency, Digeorge Syndrome, HIV infection, HTLV-BLVinfection, leukocyte adhesion deficiency syndrome, lymphopenia,phagocyte bactericidal dysfunction, severe combined immunodeficiency(SCIDs), Wiskott-Aldrich Disorder, anemia, thrombocytopenia, orhemoglobinuria.

[0943] Moreover, a polypeptide or polynucleotide of the presentinvention could also be used to modulate hemostatic (the stopping ofbleeding) or thrombolytic activity (clot formation). For example, byincreasing hemostatic or thrombolytic activity, a polynucleotide orpolypeptide of the present invention could be used to treat bloodcoagulation disorders (e.g., afibrinogenemia, factor deficiencies),blood platelet disorders (e.g. thrombocytopenia), or wounds resultingfrom trauma, surgery, or other causes. Alternatively, a polynucleotideor polypeptide of the present invention that can decrease hemostatic orthrombolytic activity could be used to inhibit or dissolve clotting.These molecules could be important in the treatment of heart attacks(infarction), strokes, or scarring.

[0944] A polynucleotide or polypeptide of the present invention may alsobe useful in treating or detecting autoimmune disorders. Many autoimmunedisorders result from inappropriate recognition of self as foreignmaterial by immune cells. This inappropriate recognition results in animmune response leading to the destruction of the host tissue.Therefore, the administration of a polypeptide or polynucleotide of thepresent invention that inhibits an immune response, particularly theproliferation, differentiation, or chemotaxis of T-cells, may be aneffective therapy in preventing autoimmune disorders.

[0945] Examples of autoimmune disorders that can be treated or detectedby the present invention include, but are not limited to: Addison'sDisease, hemolytic anemia, antiphospholipid syndrome, rheumatoidarthritis, dermatitis, allergic encephalomyelitis, glomerulonephritis,Goodpasture's Syndrome, Graves' Disease, Multiple Sclerosis, MyastheniaGravis, Neuritis, Ophthalmia, Bullous Pemphigoid, Pemphigus,Polyendocrinopathies, Purpura, Reiter's Disease, Stiff-Man Syndrome,Autoimmune Thyroiditis, Systemic Lupus Erythematosus, AutoimmunePulmonary Inflammation, Guillain-Barre Syndrome, insulin dependentdiabetes mellitis, and autoimmune inflammatory eye disease.

[0946] Similarly, allergic reactions and conditions, such as asthma(particularly allergic asthma) or other respiratory problems, may alsobe treated by a polypeptide or polynucleotide of the present invention.Moreover, these molecules can be used to treat anaphylaxis,hypersensitivity to an antigenic molecule, or blood groupincompatibility.

[0947] A polynucleotide or polypeptide of the present invention may alsobe used to treat and/or prevent organ rejection or graft-versus-hostdisease (GVHD). Organ rejection occurs by host immune cell destructionof the transplanted tissue through an immune response. Similarly, animmune response is also involved in GVHD, but, in this case, the foreigntransplanted immune cells destroy the host tissues. The administrationof a polypeptide or polynucleotide of the present invention thatinhibits an immune response, particularly the proliferation,differentiation, or chemotaxis of T-cells, may be an effective therapyin preventing organ rejection or GVHD.

[0948] Similarly, a polypeptide or polynucleotide of the presentinvention may also be used to modulate inflammation. For example, thepolypeptide or polynucleotide may inhibit the proliferation anddifferentiation of cells involved in an inflammatory response. Thesemolecules can be used to treat inflammatory conditions, both chronic andacute conditions, including inflammation associated with infection(e.g., septic shock, sepsis, or systemic inflammatory response syndrome(SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis,complement-mediated hyperacute rejection, nephritis, cytokine orchemokine induced lung injury, inflammatory bowel disease, Crohn'sdisease, or resulting from over production of cytokines (e.g., TNF orIL-1.)

[0949] Hyperproliferative Disorders

[0950] A polypeptide or polynucleotide can be used to treat or detecthyperproliferative disorders, including neoplasms. A polypeptide orpolynucleotide of the present invention may inhibit the proliferation ofthe disorder through direct or indirect interactions. Alternatively, apolypeptide or polynucleotide of the present invention may proliferateother cells which can inhibit the hyperproliferative disorder.

[0951] For example, by increasing an immune response, particularlyincreasing antigenic qualities of the hyperproliferative disorder or byproliferating, differentiating, or mobilizing T-cells,hyperproliferative disorders can be treated. This immune response may beincreased by either enhancing an existing immune response, or byinitiating a new immune response. Alternatively, decreasing an immuneresponse may also be a method of treating hyperproliferative disorders,such as a chemotherapeutic agent.

[0952] Examples of hyperproliferative disorders that can be treated ordetected by a polynucleotide or polypeptide of the present inventioninclude, but are not limited to neoplasms located in the: abdomen, bone,breast, digestive system, liver, pancreas, peritoneum, endocrine glands(adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid),eye, head and neck, nervous (central and peripheral), lymphatic system,pelvic, skin, soft tissue, spleen, thoracic, and urogenital.

[0953] Similarly, other hyperproliferative disorders can also be treatedor detected by a polynucleotide or polypeptide of the present invention.Examples of such hyperproliferative disorders include, but are notlimited to: hypergammaglobulinemia, lymphoproliferative disorders,paraproteinemias, purpura, sarcoidosis, Sezary Syndrome, Waldenstron'sMacroglobulinemia, Gaucher's Disease, histiocytosis, and any otherhyperproliferative disease, besides neoplasia, located in an organsystem listed above.

[0954] Infectious Disease

[0955] A polypeptide or polynucleotide of the present invention can beused to treat or detect infectious agents. For example, by increasingthe immune response, particularly increasing the proliferation anddifferentiation of B and/or T cells, infectious diseases may be treated.The immune response may be increased by either enhancing an existingimmune response, or by initiating a new immune response. Alternatively,the polypeptide or polynucleotide of the present invention may alsodirectly inhibit the infectious agent, without necessarily eliciting animmune response.

[0956] Viruses are one example of an infectious agent that can causedisease or symptoms that can be treated or detected by a polynucleotideor polypeptide of the present invention. Examples of viruses, include,but are not limited to the following DNA and RNA viral families:Arbovirus, Adenoviridae, Arenaviridae, Arterivirus, Birnaviridae,Bunyaviridae, Caliciviridae, Circoviridae, Coronaviridae, Flaviviridae,Hepadnaviridae (Hepatitis), Herpesviridae (such as, Cytomegalovirus,Herpes Simplex, Herpes Zoster), Mononegavirus (e.g., Paramyxoviridae,Morbillivirus, Rhabdoviridae), Orthomyxoviridae (e.g., Influenza),Papovaviridae, Parvoviridae, Picomaviridae, Poxviridae (such as Smallpoxor Vaccinia), Reoviridae (e.g., Rotavirus), Retroviridae (HTLV-I,HTLV-II, Lentivirus), and Togaviridae (e.g., Rubivirus). Viruses fallingwithin these families can cause a variety of diseases or symptoms,including, but not limited to: arthritis, bronchiollitis, encephalitis,eye infections (e.g., conjunctivitis, keratitis), chronic fatiguesyndrome, hepatitis (A, B, C, E, Chronic Active, Delta), meningitis,opportunistic infections (e.g., AIDS), pneumonia, Burkitt's Lymphoma,chickenpox , hemorrhagic fever, Measles, Mumps, Parainfluenza, Rabies,the common cold, Polio, leukemia, Rubella, sexually transmitteddiseases, skin diseases (e.g., Kaposi's, warts), and viremia. Apolypeptide or polynucleotide of the present invention can be used totreat or detect any of these symptoms or diseases.

[0957] Similarly, bacterial or fungal agents that can cause disease orsymptoms and that can be treated or detected by a polynucleotide orpolypeptide of the present invention include, but not limited to, thefollowing Gram-Negative and Gram-positive bacterial families and fungi:Actinomycetales (e.g., Corynebacterium, Mycobacterium. Norcardia),Aspergillosis, Bacillaceae (e.g., Anthrax, Clostridium), Bacteroidaceae,Blastomycosis, Bordetella, Borrelia, Brucellosis, Candidiasis,Campylobacter, Coccidioidomycosis, Cryptococcosis, Dermatocycoses,Enterobacteriaceae (Klebsiella, Salmonella, Serratia, Yersinia),Erysipelothrix, Helicobacter, Legionellosis, Leptospirosis, Listeria,Mycoplasmatales, Neisseriaceae (e.g., Acinetobacter, Gonorrhea,Menigococcal), Pasteurellacea Infections (e.g., Actinobacillus,Heamophilus, Pasteurella), Pseudomonas, Rickettsiaceae. Chlamydiaceae,Syphilis, and Staphylococcal. These bacterial or fungal families cancause the following diseases or symptoms, including, but not limited to:bacteremia, endocarditis, eye infections (conjunctivitis, tuberculosis,uveitis), gingivitis, opportunistic infections (e.g., AIDS relatedinfections), paronychia, prosthesis-related infections, Reiter'sDisease, respiratory tract infections, such as Whooping Cough orEmpyema, sepsis, Lyme Disease, Cat-Scratch Disease, Dysentery,Paratyphoid Fever, food poisoning, Typhoid, pneumonia, Gonorrhea,meningitis, Chlamydia, Syphilis, Diphtheria, Leprosy, Paratuberculosis,Tuberculosis, Lupus, Botulism, gangrene, tetanus, impetigo, RheumaticFever, Scarlet Fever, sexually transmitted diseases, skin diseases(e.g., cellulitis, dermatocycoses), toxemia, urinary tract infections,wound infections. A polypeptide or polynucleotide of the presentinvention can be used to treat or detect any of these symptoms ordiseases.

[0958] Moreover, parasitic agents causing disease or symptoms that canbe treated or detected by a polynucleotide or polypeptide of the presentinvention include, but not limited to, the following families:Amebiasis, Babesiosis, Coccidiosis, Cryptosporidiosis, Dientamoebiasis,Dourine, Ectoparasitic, Giardiasis, Helminthiasis, Leishmaniasis,Theileriasis, Toxoplasmosis, Trypanosomiasis, and Trichomonas. Theseparasites can cause a variety of diseases or symptoms, including, butnot limited to: Scabies, Trombiculiasis, eye infections, intestinaldisease (e.g., dysentery, giardiasis), liver disease, lung disease,opportunistic infections (e.g., AIDS related), Malaria, pregnancycomplications, and toxoplasmosis. A polypeptide or polynucleotide of thepresent invention can be used to treat or detect any of these symptomsor diseases.

[0959] Preferably, treatment using a polypeptide or polynucleotide ofthe present invention could either be by administering an effectiveamount of a polypeptide to the patient, or by removing cells from thepatient, supplying the cells with a polynucleotide of the presentinvention, and returning the engineered cells to the patient (ex-vivotherapy). Moreover, the polypeptide or polynucleotide of the presentinvention can be used as an antigen in a vaccine to raise an immuneresponse against infectious disease.

[0960] Regeneration

[0961] A polynucleotide or polypeptide of the present invention can beused to differentiate, proliferate, and attract cells, leading to theregeneration of tissues. (See, Science 276:59-87 (1997).) Theregeneration of tissues could be used to repair, replace, or protecttissue damaged by congenital defects, trauma (wounds, burns, incisions,or ulcers), age, disease (e.g. osteoporosis, osteocarthritis,periodontal disease, liver failure), surgery, including cosmetic plasticsurgery, fibrosis, reperfusion injury, or systemic cytokine damage.

[0962] Tissues that could be regenerated using the present inventioninclude organs (e.g., pancreas, liver, intestine, kidney, skin,endothelium), muscle (smooth, skeletal or cardiac), vascular (includingvascular endothelium), nervous, hematopoietic, and skeletal (bone,cartilage, tendon, and ligament) tissue. Preferably, regeneration occurswithout or decreased scarring. Regeneration also may includeangiogenesis.

[0963] Moreover, a polynucleotide or polypeptide of the presentinvention may increase regeneration of tissues difficult to heal. Forexample, increased tendon/ligament regeneration would quicken recoverytime after damage. A polynucleotide or polypeptide of the presentinvention could also be used prophylactically in an effort to avoiddamage. Specific diseases that could be treated include of tendinitis,carpal tunnel syndrome, and other tendon or ligament defects. A furtherexample of tissue regeneration of non-healing wounds includes pressureulcers, ulcers associated with vascular insufficiency, surgical, andtraumatic wounds.

[0964] Similarly, nerve and brain tissue could also be regenerated byusing a polynucleotide or polypeptide of the present invention toproliferate and differentiate nerve cells. Diseases that could betreated using this method include central and peripheral nervous systemdiseases, neuropathies, or mechanical and traumatic disorders (e.g.,spinal cord disorders, head trauma, cerebrovascular disease, and stoke).Specifically, diseases associated with peripheral nerve injuries,peripheral neuropathy (e.g., resulting from chemotherapy or othermedical therapies), localized neuropathies, and central nervous systemdiseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington'sdisease, amyotrophic lateral sclerosis, and Shy-Drager syndrome), couldall be treated using the polynucleotide or polypeptide of the presentinvention.

[0965] Chemotaxis

[0966] A polynucleotide or polypeptide of the present invention may havechemotaxis activity. A chemotaxic molecule attracts or mobilizes cells(e.g., monocytes, fibroblasts, neutrophils, T-cells, mast cells,eosinophils, epithelial and/or endothelial cells) to a particular sitein the body, such as inflammation, infection, or site ofhyperproliferation. The mobilized cells can then fight off and/or healthe particular trauma or abnormality.

[0967] A polynucleotide or polypeptide of the present invention mayincrease chemotaxic activity of particular cells. These chemotacticmolecules can then be used to treat inflammation, infection,hyperproliferative disorders, or any immune system disorder byincreasing the number of cells targeted to a particular location in thebody. For example, chemotaxic molecules can be used to treat wounds andother trauma to tissues by attracting immune cells to the injuredlocation. Chemotactic molecules of the present invention can alsoattract fibroblasts, which can be used to treat wounds.

[0968] It is also contemplated that a polynucleotide or polypeptide ofthe present invention may inhibit chemotactic activity. These moleculescould also be used to treat disorders. Thus, a polynucleotide orpolypeptide of the present invention could be used as an inhibitor ofchemotaxis.

[0969] Binding Activity

[0970] A polypeptide of the present invention may be used to screen formolecules that bind to the polypeptide or for molecules to which thepolypeptide binds. The binding of the polypeptide and the molecule mayactivate (agonist), increase, inhibit (antagonist), or decrease activityof the polypeptide or the molecule bound. Examples of such moleculesinclude antibodies, oligonucleotides, proteins (e.g., receptors),orsmall molecules.

[0971] Preferably, the molecule is closely related to the natural ligandof the polypeptide, e.g., a fragment of the ligand, or a naturalsubstrate, a ligand, a structural or functional mimetic. (See, Coliganet al., Current Protocols in Immunology 1(2):Chapter 5 (1991).)Similarly, the molecule can be closely related to the natural receptorto which the polypeptide binds, or at least, a fragment of the receptorcapable of being bound by the polypeptide (e.g., active site). In eithercase, the molecule can be rationally designed using known techniques.

[0972] Preferably, the screening for these molecules involves producingappropriate cells which express the polypeptide, either as a secretedprotein or on the cell membrane. Preferred cells include cells frommammals, yeast, Drosophila, or E. coli. Cells expressing the polypeptide(or cell membrane containing the expressed polypeptide) are thenpreferably contacted with a test compound potentially containing themolecule to observe binding, stimulation, or inhibition of activity ofeither the polypeptide or the molecule.

[0973] The assay may simply test binding of a candidate compound to thepolypeptide, wherein binding is detected by a label, or in an assayinvolving competition with a labeled competitor. Further, the assay maytest whether the candidate compound results in a signal generated bybinding to the polypeptide.

[0974] Alternatively, the assay can be carried out using cell-freepreparations, polypeptide/molecule affixed to a solid support, chemicallibraries, or natural product mixtures. The assay may also simplycomprise the steps of mixing a candidate compound with a solutioncontaining a polypeptide, measuring polypeptide/molecule activity orbinding, and comparing the polypeptide/molecule activity or binding to astandard.

[0975] Preferably, an ELISA assay can measure polypeptide level oractivity in a sample (e.g., biological sample) using a monoclonal orpolyclonal antibody. The antibody can measure polypeptide level oractivity by either binding, directly or indirectly, to the polypeptideor by competing with the polypeptide for a substrate.

[0976] All of these above assays can be used as diagnostic or prognosticmarkers. The molecules discovered using these assays can be used totreat disease or to bring about a particular result in a patient (e.g.,blood vessel growth) by activating or inhibiting thepolypeptide/molecule. Moreover, the assays can discover agents which mayinhibit or enhance the production of the polypeptide from suitablymanipulated cells or tissues.

[0977] Therefore, the invention includes a method of identifyingcompounds which bind to a polypeptide of the invention comprising thesteps of: (a) incubating a candidate binding compound with a polypeptideof the invention; and (b) determining if binding has occurred. Moreover,the invention includes a method of identifying agonists/antagonistscomprising the steps of: (a) incubating a candidate compound with apolypeptide of the invention, (b) assaying a biological activity, and(b) determining if a biological activity of the polypeptide has beenaltered.

[0978] Other Activities

[0979] A polypeptide or polynucleotide of the present invention may alsoincrease or decrease the differentiation or proliferation of embryonicstem cells, besides, as discussed above, hematopoietic lineage.

[0980] A polypeptide or polynucleotide of the present invention may alsobe used to modulate mammalian characteristics, such as body height,weight, hair color, eye color, skin, percentage of adipose tissue,pigmentation, size, and shape (e.g., cosmetic surgery). Similarly, apolypeptide or polynucleotide of the present invention may be used tomodulate mammalian metabolism affecting catabolism, anabolism,processing, utilization, and storage of energy.

[0981] A polypeptide or polynucleotide of the present invention may beused to change a mammal's mental state or physical state by influencingbiorhythms, caricadic rhythms, depression (including depressivedisorders), tendency for violence, tolerance for pain, reproductivecapabilities (preferably by Activin or Inhibin-like activity), hormonalor endocrine levels, appetite, libido, memory, stress, or othercognitive qualities.

[0982] A polypeptide or polynucleotide of the present invention may alsobe used as a food additive or preservative, such as to increase ordecrease storage capabilities, fat content, lipid, protein,carbohydrate, vitamins, minerals, cofactors or other nutritionalcomponents.

[0983] Other Preferred Embodiments

[0984] Other preferred embodiments of the claimed invention include anisolated nucleic acid molecule comprising a nucleotide sequence which isat least 95% identical to a sequence of at least about 50 contiguousnucleotides in the nucleotide sequence of SEQ ID NO:X wherein X is anyinteger as defined in Table 1.

[0985] Also preferred is a nucleic acid molecule wherein said sequenceof contiguous nucleotides is included in the nucleotide sequence of SEQID NO:X in the range of positions beginning with the nucleotide at aboutthe position of the 5′ Nucleotide of the Clone Sequence and ending withthe nucleotide at about the position of the 3′ Nucleotide of the CloneSequence as defined for SEQ ID NO:X in Table 1.

[0986] Also preferred is a nucleic acid molecule wherein said sequenceof contiguous nucleotides is included in the nucleotide sequence of SEQID NO:X in the range of positions beginning with the nucleotide at aboutthe position of the 5′ Nucleotide of the Start Codon and ending with thenucleotide at about the position of the 3′ Nucleotide of the CloneSequence as defined for SEQ ID NO:X in Table 1.

[0987] Similarly preferred is a nucleic acid molecule wherein saidsequence of contiguous nucleotides is included in the nucleotidesequence of SEQ ID NO:X in the range of positions beginning with thenucleotide at about the position of the 5′ Nucleotide of the First AminoAcid of the Signal Peptide and ending with the nucleotide at about theposition of the 3′ Nucleotide of the Clone Sequence as defined for SEQID NO:X in Table 1.

[0988] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to a sequence of atleast about 150 contiguous nucleotides in the nucleotide sequence of SEQID NO:X.

[0989] Further preferred is an isolated nucleic acid molecule comprisinga nucleotide sequence which is at least 95% identical to a sequence ofat least about 500 contiguous nucleotides in the nucleotide sequence ofSEQ ID NO:X.

[0990] A further preferred embodiment is a nucleic acid moleculecomprising a nucleotide sequence which is at least 95% identical to thenucleotide sequence of SEQ ID NO:X beginning with the nucleotide atabout the position of the 5′ Nucleotide of the First Amino Acid of theSignal Peptide and ending with the nucleotide at about the position ofthe 3′ Nucleotide of the Clone Sequence as defined for SEQ ID NO:X inTable 1.

[0991] A further preferred embodiment is an isolated nucleic acidmolecule comprising a nucleotide sequence which is at least 95%identical to the complete nucleotide sequence of SEQ ID NO:X.

[0992] Also preferred is an isolated nucleic acid molecule whichhybridizes under stringent hybridization conditions to a nucleic acidmolecule, wherein said nucleic acid molecule which hybridizes does nothybridize under stringent hybridization conditions to a nucleic acidmolecule having a nucleotide sequence consisting of only A residues orof only T residues.

[0993] Also preferred is a composition of matter comprising a DNAmolecule which comprises a human cDNA clone identified by a cDNA CloneIdentifier in Table 1, which DNA molecule is contained in the materialdeposited with the American Type Culture Collection and given the ATCCDeposit Number shown in Table 1 for said cDNA Clone Identifier.

[0994] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to a sequence of atleast 50 contiguous nucleotides in the nucleotide sequence of a humancDNA clone identified by a cDNA Clone Identifier in Table 1, which DNAmolecule is contained in the deposit given the ATCC Deposit Number shownin Table 1.

[0995] Also preferred is an isolated nucleic acid molecule, wherein saidsequence of at least 50 contiguous nucleotides is included in thenucleotide sequence of the complete open reading frame sequence encodedby said human cDNA clone.

[0996] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to sequence of atleast 150 contiguous nucleotides in the nucleotide sequence encoded bysaid human cDNA clone.

[0997] A further preferred embodiment is an isolated nucleic acidmolecule comprising a nucleotide sequence which is at least 95%identical to sequence of at least 500 contiguous nucleotides in thenucleotide sequence encoded by said human cDNA clone.

[0998] A further preferred embodiment is an isolated nucleic acidmolecule comprising a nucleotide sequence which is at least 95%identical to the complete nucleotide sequence encoded by said human cDNAclone.

[0999] A further preferred embodiment is a method for detecting in abiological sample a nucleic acid molecule comprising a nucleotidesequence which is at least 95% identical to a sequence of at least 50contiguous nucleotides in a sequence selected from the group consistingof: a nucleotide sequence of SEQ ID NO:X wherein X is any integer asdefined in Table 1; and a nucleotide sequence encoded by a human cDNAclone identified by a cDNA Clone Identifier in Table 1 and contained inthe deposit with the ATCC Deposit Number shown for said cDNA clone inTable 1; which method comprises a step of comparing a nucleotidesequence of at least one nucleic acid molecule in said sample with asequence selected from said group and determining whether the sequenceof said nucleic acid molecule in said sample is at least 95% identicalto said selected sequence.

[1000] Also preferred is the above method wherein said step of comparingsequences comprises determining the extent of nucleic acid hybridizationbetween nucleic acid molecules in said sample and a nucleic acidmolecule comprising said sequence selected from said group. Similarly,also preferred is the above method wherein said step of comparingsequences is performed by comparing the nucleotide sequence determinedfrom a nucleic acid molecule in said sample with said sequence selectedfrom said group. The nucleic acid molecules can comprise DNA moleculesor RNA molecules.

[1001] A further preferred embodiment is a method for identifying thespecies, tissue or cell type of a biological sample which methodcomprises a step of detecting nucleic acid molecules in said sample, ifany, comprising a nucleotide sequence that is at least 95% identical toa sequence of at least 50 contiguous nucleotides in a sequence selectedfrom the group consisting of: a nucleotide sequence of SEQ ID NO:Xwherein X is any integer as defined in Table 1; and a nucleotidesequence encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1.

[1002] The method for identifying the species, tissue or cell type of abiological sample can comprise a step of detecting nucleic acidmolecules comprising a nucleotide sequence in a panel of at least twonucleotide sequences, wherein at least one sequence in said panel is atleast 95% identical to a sequence of at least 50 contiguous nucleotidesin a sequence selected from said group.

[1003] Also preferred is a method for diagnosing in a subject apathological condition associated with abnormal structure or expressionof a gene encoding a secreted protein identified in Table 1, whichmethod comprises a step of detecting in a biological sample obtainedfrom said subject nucleic acid molecules, if any, comprising anucleotide sequence that is at least 95% identical to a sequence of atleast 50 contiguous nucleotides in a sequence selected from the groupconsisting of: a nucleotide sequence of SEQ ID NO:X wherein X is anyinteger as defined in Table 1; and a nucleotide sequence encoded by ahuman cDNA clone identified by a cDNA Clone Identifier in Table 1 andcontained in the deposit with the ATCC Deposit Number shown for saidcDNA clone in Table 1.

[1004] The method for diagnosing a pathological condition can comprise astep of detecting nucleic acid molecules comprising a nucleotidesequence in a panel of at least two nucleotide sequences, wherein atleast one sequence in said panel is at least 95% identical to a sequenceof at least 50 contiguous nucleotides in a sequence selected from saidgroup.

[1005] Also preferred is a composition of matter comprising isolatednucleic acid molecules wherein the nucleotide sequences of said nucleicacid molecules comprise a panel of at least two nucleotide sequences,wherein at least one sequence in said panel is at least 95% identical toa sequence of at least 50 contiguous nucleotides in a sequence selectedfrom the group consisting of: a nucleotide sequence of SEQ ID NO:Xwherein X is any integer as defined in Table 1; and a nucleotidesequence encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1. The nucleic acid moleculescan comprise DNA molecules or RNA molecules.

[1006] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 90% identical to a sequence of at least about 10contiguous amino acids in the amino acid sequence of SEQ ID NO:Y whereinY is any integer as defined in Table 1.

[1007] Also preferred is a polypeptide, wherein said sequence ofcontiguous amino acids is included in the amino acid sequence of SEQ IDNO:Y in the range of positions beginning with the residue at about theposition of the First Amino Acid of the Secreted Portion and ending withthe residue at about the Last Amino Acid of the Open Reading Frame asset forth for SEQ ID NO:Y in Table 1.

[1008] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to a sequence of at least about 30contiguous amino acids in the amino acid sequence of SEQ ID NO:Y.

[1009] Further preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to a sequence of at least about 100contiguous amino acids in the amino acid sequence of SEQ ID NO:Y.

[1010] Further preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to the complete amino acid sequenceof SEQ ID NO:Y.

[1011] Further preferred is an isolated polypeptide comprising an aminoacid sequence at least 90% identical to a sequence of at least about 10contiguous amino acids in the complete amino acid sequence of a secretedprotein encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1.

[1012] Also preferred is a polypeptide wherein said sequence ofcontiguous amino acids is included in the amino acid sequence of asecreted portion of the secreted protein encoded by a human cDNA cloneidentified by a cDNA Clone Identifier in Table 1 and contained in thedeposit with the ATCC Deposit Number shown for said cDNA clone in Table1.

[1013] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to a sequence of at least about 30contiguous amino acids in the amino acid sequence of the secretedportion of the protein encoded by a human cDNA clone identified by acDNA Clone Identifier in Table 1 and contained in the deposit with theATCC Deposit Number shown for said cDNA clone in Table 1.

[1014] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to a sequence of at least about 100contiguous amino acids in the amino acid sequence of the secretedportion of the protein encoded by a human cDNA clone identified by acDNA Clone Identifier in Table 1 and contained in the deposit with theATCC Deposit Number shown for said cDNA clone in Table 1.

[1015] Also preferred is an isolated polypeptide comprising an aminoacid sequence at least 95% identical to the amino acid sequence of thesecreted portion of the protein encoded by a human cDNA clone identifiedby a cDNA Clone Identifier in Table 1 and contained in the deposit withthe ATCC Deposit Number shown for said cDNA clone in Table 1.

[1016] Further preferred is an isolated antibody which bindsspecifically to a polypeptide comprising an amino acid sequence that isat least 90% identical to a sequence of at least 10 contiguous aminoacids in a sequence selected from the group consisting of: an amino acidsequence of SEQ ID NO:Y wherein Y is any integer as defined in Table 1;and a complete amino acid sequence of a protein encoded by a human cDNAclone identified by a cDNA Clone Identifier in Table 1 and contained inthe deposit with the ATCC Deposit Number shown for said cDNA clone inTable 1.

[1017] Further preferred is a method for detecting in a biologicalsample a polypeptide comprising an amino acid sequence which is at least90% identical to a sequence of at least 10 contiguous amino acids in asequence selected from the group consisting of: an amino acid sequenceof SEQ ID NO:Y wherein Y is any integer as defined in Table 1; and acomplete amino acid sequence of a protein encoded by a human cDNA cloneidentified by a cDNA Clone Identifier in Table 1 and contained in thedeposit with the ATCC Deposit Number shown for said cDNA clone in Table1; which method comprises a step of comparing an amino acid sequence ofat least one polypeptide molecule in said sample with a sequenceselected from said group and determining whether the sequence of saidpolypeptide molecule in said sample is at least 90% identical to saidsequence of at least 10 contiguous amino acids.

[1018] Also preferred is the above method wherein said step of comparingan amino acid sequence of at least one polypeptide molecule in saidsample with a sequence selected from said group comprises determiningthe extent of specific binding of polypeptides in said sample to anantibody which binds specifically to a polypeptide comprising an aminoacid sequence that is at least 90% identical to a sequence of at least10 contiguous amino acids in a sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of aprotein encoded by a human cDNA clone identified by a cDNA CloneIdentifier in Table 1 and contained in the deposit with the ATCC DepositNumber shown for said cDNA clone in Table 1.

[1019] Also preferred is the above method wherein said step of comparingsequences is performed by comparing the amino acid sequence determinedfrom a polypeptide molecule in said sample with said sequence selectedfrom said group.

[1020] Also preferred is a method for identifying the species, tissue orcell type of a biological sample which method comprises a step ofdetecting polypeptide molecules in said sample, if any, comprising anamino acid sequence that is at least 90% identical to a sequence of atleast 10 contiguous amino acids in a sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of asecreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[1021] Also preferred is the above method for identifying the species,tissue or cell type of a biological sample, which method comprises astep of detecting polypeptide molecules comprising an amino acidsequence in a panel of at least two amino acid sequences, wherein atleast one sequence in said panel is at least 90% identical to a sequenceof at least 10 contiguous amino acids in a sequence selected from theabove group.

[1022] Also preferred is a method for diagnosing in a subject apathological condition associated with abnormal structure or expressionof a gene encoding a secreted protein identified in Table 1, whichmethod comprises a step of detecting in a biological sample obtainedfrom said subject polypeptide molecules comprising an amino acidsequence in a panel of at least two amino acid sequences, wherein atleast one sequence in said panel is at least 90% identical to a sequenceof at least 10 contiguous amino acids in a sequence selected from thegroup consisting of: an amino acid sequence of SEQ ID NO:Y wherein Y isany integer as defined in Table 1; and a complete amino acid sequence ofa secreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[1023] In any of these methods, the step of detecting said polypeptidemolecules includes using an antibody.

[1024] Also preferred is an isolated nucleic acid molecule comprising anucleotide sequence which is at least 95% identical to a nucleotidesequence encoding a polypeptide wherein said polypeptide comprises anamino acid sequence that is at least 90% identical to a sequence of atleast 10 contiguous amino acids in a sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of asecreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[1025] Also preferred is an isolated nucleic acid molecule, wherein saidnucleotide sequence encoding a polypeptide has been optimized forexpression of said polypeptide in a prokaryotic host.

[1026] Also preferred is an isolated nucleic acid molecule, wherein saidpolypeptide comprises an amino acid sequence selected from the groupconsisting of: an amino acid sequence of SEQ ID NO:Y wherein Y is anyinteger as defined in Table 1; and a complete amino acid sequence of asecreted protein encoded by a human cDNA clone identified by a cDNAClone Identifier in Table 1 and contained in the deposit with the ATCCDeposit Number shown for said cDNA clone in Table 1.

[1027] Further preferred is a method of making a recombinant vectorcomprising inserting any of the above isolated nucleic acid moleculeinto a vector. Also preferred is the recombinant vector produced by thismethod. Also preferred is a method of making a recombinant host cellcomprising introducing the vector into a host cell, as well as therecombinant host cell produced by this method.

[1028] Also preferred is a method of making an isolated polypeptidecomprising culturing this recombinant host cell under conditions suchthat said polypeptide is expressed and recovering said polypeptide. Alsopreferred is this method of making an isolated polypeptide, wherein saidrecombinant host cell is a eukaryotic cell and said polypeptide is asecreted portion of a human secreted protein comprising an amino acidsequence selected from the group consisting of: an amino acid sequenceof SEQ ID NO:Y beginning with the residue at the position of the FirstAmino Acid of the Secreted Portion of SEQ ID NO:Y wherein Y is aninteger set forth in Table 1 and said position of the First Amino Acidof the Secreted Portion of SEQ ID NO:Y is defined in Table 1; and anamino acid sequence of a secreted portion of a protein encoded by ahuman cDNA clone identified by a cDNA Clone Identifier in Table 1 andcontained in the deposit with the ATCC Deposit Number shown for saidcDNA clone in Table 1. The isolated polypeptide produced by this methodis also preferred.

[1029] Also preferred is a method of treatment of an individual in needof an increased level of a secreted protein activity, which methodcomprises administering to such an individual a pharmaceuticalcomposition comprising an amount of an isolated polypeptide,polynucleotide, or antibody of the claimed invention effective toincrease the level of said protein activity in said individual.

[1030] Having generally described the invention, the same will be morereadily understood by reference to the following examples, which areprovided by way of illustration and are not intended as limiting.

EXAMPLES Example 1 Isolation of a Selected cDNA Clone from the DepositedSample

[1031] Each cDNA clone in a cited ATCC deposit is contained in a plasmidvector. Table 1 identifies the vectors used to construct the cDNAlibrary from which each clone was isolated. In many cases, the vectorused to construct the library is a phage vector from which a plasmid hasbeen excised. The table immediately below correlates the related plasmidfor each phage vector used in constructing the cDNA library. Forexample, where a particular clone is identified in Table 1 as beingisolated in the vector “Lambda Zap,” the corresponding deposited cloneis in “pBluescript.” Vector Used to Construct Library CorrespondingDeposited Plasmid Lambda Zap pBluescript (pBS) Uni-Zap XR pBluescript(pBS) Zap Express pBK lafmid BA plafmid BA pSport1 pSport1 pCMVSport 2.0pCMVSport 2.0 pCMVSport 3.0 pCMVSport 3.0 pCR ®2.1 pCR ®2.1

[1032] Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636),Uni-Zap XR (U.S. Pat. Nos. 5,128,256 and 5,286,636), Zap Express (U.S.Pat. Nos. 5,128,256 and 5,286,636), pBluescript (pBS) (Short, J. M. etal., Nucleic Acids Res. 16:7583-7600 (1988); Alting-Mees, M. A. andShort, J. M., Nucleic Acids Res. 17:9494 (1989)) and pBK (Alting-Mees,M. A. et al., Strategies 5:58-61 (1992)) are commercially available fromStratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla,Calif., 92037. pBS contains an ampicillin resistance gene and pBKcontains a neomycin resistance gene. Both can be transformed into E.coli strain XL-1 Blue, also available from Stratagene. pBS comes in 4forms SK+, SK−, KS+ and KS. The S and K refers to the orientation of thepolylinker to the T7 and T3 primer sequences which flank the polylinkerregion (“S” is for SacI and “K” is for KpnI which are the first sites oneach respective end of the linker). “+” or “−” refer to the orientationof the f1 origin of replication (“ori”), such that in one orientation,single stranded rescue initiated from the f1 ori generates sense strandDNA and in the other, antisense.

[1033] Vectors pSport1, pCMVSport 2.0 and pCMVSport 3.0, were obtainedfrom Life Technologies, Inc., P. O. Box 6009, Gaithersburg, Md. 20897.All Sport vectors contain an ampicillin resistance gene and may betransformed into E. coli strain DH10B, also available from LifeTechnologies. (See, for instance, Gruber, C. E., et al., Focus 15:59(1993).) Vector lafmid BA (Bento Soares, Columbia University, NY)contains an ampicillin resistance gene and can be transformed into E.coli strain XL-1 Blue. Vector pCR®2.1, which is available fromInvitrogen, 1600 Faraday Avenue, Carlsbad, Calif. 92008, contains anampicillin resistance gene and may be transformed into E. coli strainDH10B, available from Life Technologies. (See, for instance, Clark, J.M., Nuc. Acids Res. 16:9677-9686 (1988) and Mead, D. et al.,Bio/Technology 9: (1991).) Preferably, a polynucleotide of the presentinvention does not comprise the phage vector sequences identified forthe particular clone in Table 1, as well as the corresponding plasmidvector sequences designated above.

[1034] The deposited material in the sample assigned the ATCC DepositNumber cited in Table 1 for any given cDNA clone also may contain one ormore additional plasmids, each comprising a cDNA clone different fromthat given clone. Thus, deposits sharing the same ATCC Deposit Numbercontain at least a plasmid for each cDNA clone identified in Table 1.Typically, each ATCC deposit sample cited in Table 1 comprises a mixtureof approximately equal amounts (by weight) of about 50 plasmid DNAs,each containing a different cDNA clone; but such a deposit sample mayinclude plasmids for more or less than 50 cDNA clones, up to about 500cDNA clones.

[1035] Two approaches can be used to isolate a particular clone from thedeposited sample of plasmid DNAs cited for that clone in Table 1. First,a plasmid is directly isolated by screening the clones using apolynucleotide probe corresponding to SEQ ID NO:X.

[1036] Particularly, a specific polynucleotide with 30-40 nucleotides issynthesized using an Applied Biosystems DNA synthesizer according to thesequence reported. The oligonucleotide is labeled, for instance, with³²P-γ-ATP using T4 polynucleotide kinase and purified according toroutine methods. (E.g., Maniatis et al., Molecular Cloning: A LaboratoryManual, Cold Spring Harbor Press, Cold Spring, N.Y. (1982).) The plasmidmixture is transformed into a suitable host, as indicated above (such asXL-1 Blue (Stratagene)) using techniques known to those of skill in theart, such as those provided by the vector supplier or in relatedpublications or patents cited above. The transformants are plated on1.5% agar plates (containing the appropriate selection agent, e.g.,ampicillin) to a density of about 150 transformants (colonies) perplate. These plates are screened using Nylon membranes according toroutine methods for bacterial colony screening (e.g., Sambrook et al.,Molecular Cloning: A Laboratory Manual, 2nd Edit., (1989), Cold SpringHarbor Laboratory Press, pages 1.93 to 1.104), or other techniques knownto those of skill in the art.

[1037] Alternatively, two primers of 17-20 nucleotides derived from bothends of the SEQ ID NO:X (i.e., within the region of SEQ ID NO:X boundedby the 5′ NT and the 3′ NT of the clone defined in Table 1) aresynthesized and used to amplify the desired cDNA using the depositedcDNA plasmid as a template. The polymerase chain reaction is carried outunder routine conditions, for instance, in 25 μl of reaction mixturewith 0.5 ug of the above cDNA template. A convenient reaction mixture is1.5-5 mM MgCl₂, 0.01% (w/v) gelatin, 20 μM each of dATP, dCTP, dGTP,dTTP, 25 pmol of each primer and 0.25 Unit of Taq polymerase. Thirtyfive cycles of PCR (denaturation at 94° C. for 1 min; annealing at 55°C. for 1 min; elongation at 72° C. for 1 min) are performed with aPerkin-Elmer Cetus automated thermal cycler. The amplified product isanalyzed by agarose gel electrophoresis and the DNA band with expectedmolecular weight is excised and purified. The PCR product is verified tobe the selected sequence by subcloning and sequencing the DNA product.

[1038] Several methods are available for the identification of the 5′ or3′ non-coding portions of a gene which may not be present in thedeposited clone. These methods include but are not limited to, filterprobing, clone enrichment using specific probes, and protocols similaror identical to 5′ and 3′ “RACE” protocols which are well known in theart. For instance, a method similar to 5′ RACE is available forgenerating the missing 5′ end of a desired full-length transcript.(Fromont-Racine et al., Nucleic Acids Res. 21(7):1683-1684 (1993).)

[1039] Briefly, a specific RNA oligonucleotide is ligated to the 5′ endsof a population of RNA presumably containing full-length gene RNAtranscripts. A primer set containing a primer specific to the ligatedRNA oligonucleotide and a primer specific to a known sequence of thegene of interest is used to PCR amplify the 5′ portion of the desiredfull-length gene. This amplified product may then be sequenced and usedto generate the full length gene.

[1040] This above method starts with total RNA isolated from the desiredsource, although poly-A+ RNA can be used. The RNA preparation can thenbe treated with phosphatase if necessary to eliminate 5′ phosphategroups on degraded or damaged RNA which may interfere with the later RNAligase step. The phosphatase should then be inactivated and the RNAtreated with tobacco acid pyrophosphatase in order to remove the capstructure present at the 5′ ends of messenger RNAs. This reaction leavesa 5′ phosphate group at the 5′ end of the cap cleaved RNA which can thenbe ligated to an RNA oligonucleotide using T4 RNA ligase.

[1041] This modified RNA preparation is used as a template for firststrand cDNA synthesis using a gene specific oligonucleotide. The firststrand synthesis reaction is used as a template for PCR amplification ofthe desired 5′ end using a primer specific to the ligated RNAoligonucleotide and a primer specific to the known sequence of the geneof interest. The resultant product is then sequenced and analyzed toconfirm that the 5′ end sequence belongs to the desired gene.

Example 2 Isolation of Genomic Clones Corresponding to a Polynucleotide

[1042] A human genomic P1 library (Genomic Systems, Inc.) is screened byPCR using primers selected for the cDNA sequence corresponding to SEQ IDNO:X., according to the method described in Example 1. (See also,Sambrook.)

Example 3 Tissue Distribution of Polypeptide

[1043] Tissue distribution of mRNA expression of polynucleotides of thepresent invention is determined using protocols for Northern blotanalysis, described by, among others, Sambrook et al. For example, acDNA probe produced by the method described in Example 1 is labeled withP³² using the rediprime™ DNA labeling system (Amersham Life Science),according to manufacturer's instructions. After labeling, the probe ispurified using CHROMA SPIN-100™ column (Clontech Laboratories, Inc.),according to manufacturer's protocol number PT 1200-1. The purifiedlabeled probe is then used to examine various human tissues for mRNAexpression.

[1044] Multiple Tissue Northern (MTN) blots containing various humantissues (H) or human immune system tissues (IM) (Clontech) are examinedwith the labeled probe using ExpressHyb™ hybridization solution(Clontech) according to manufacturer's mounted and exposed to film at−70° C. overnight, and the films developed according to standardprocedures.

Example 4 Chromosomal Mapping of the Polynucleotides

[1045] An oligonucleotide primer set is designed according to thesequence at the 5′ end of SEQ ID NO:X. This primer preferably spansabout 100 nucleotides. This primer set is then used in a polymerasechain reaction under the following set of conditions: 30 seconds, 95°C.; 1 minute, 56° C.; 1 minute, 70° C. This cycle is repeated 32 timesfollowed by one 5 minute cycle at 70° C. Human, mouse, and hamster DNAis used as template in addition to a somatic cell hybrid panelcontaining individual chromosomes or chromosome fragments (Bios, Inc).The reactions is analyzed on either 8% polyacrylamide gels or 3.5%agarose gels. Chromosome mapping is determined by the presence of anapproximately 100 bp PCR fragment in the particular somatic cell hybrid.

Example 5 Bacterial Expression of a Polypeptide

[1046] A polynucleotide encoding a polypeptide of the present inventionis amplified using PCR oligonucleotide primers corresponding to the 5′and 3′ ends of the DNA sequence, as outlined in Example 1, to synthesizeinsertion fragments. The primers used to amplify the cDNA insert shouldpreferably contain restriction sites, such as BamHI and XbaI, at the 5′end of the primers in order to clone the amplified product into theexpression vector. For example, BamHI and XbaI correspond to therestriction enzyme sites on the bacterial expression vector pQE-9.(Qiagen, Inc., Chatsworth, Calif.). This plasmid vector encodesantibiotic resistance (Ampr), a bacterial origin of replication (ori),an IPTG-regulatable promoter/operator (P/0), a ribosome binding site(RBS), a 6-histidine tag (6-His), and restriction enzyme cloning sites.

[1047] The pQE-9 vector is digested with BamHI and XbaI and theamplified fragment is ligated into the pQE-9 vector maintaining thereading frame initiated at the bacterial RBS The ligation mixture isthen used to transform the E. coli strain M15/rep4 (Qiagen, Inc.) whichcontains multiple copies of the plasmid pREP4, which expresses the lacIrepressor and also confers kanamycin resistance (Kan^(r)). Transformantsare identified by their ability to grow on LB plates andampicillin/kanamycin resistant colonies are selected. Plasmid DNA isisolated and confirmed by restriction analysis.

[1048] Clones containing the desired constructs are grown overnight(O/N) in liquid culture in LB media supplemented with both Amp (100ug/m) and Kan (25 ug/ml). The O/N culture is used to inoculate a largeculture at a ratio of 1:100 to 1:250. The cells are grown to an opticaldensity 600 (O.D.⁶⁰⁰) of between 0.4 and 0.6. IPTG(Isopropyl-B-D-thiogalacto pyranoside) is then added to a finalconcentration of 1 mM. IPTG induces by inactivating the lacI repressor,clearing the P/O leading to increased gene expression.

[1049] Cells are grown for an extra 3 to 4 hours. Cells are thenharvested by centrifugation (20 mins at 6000×g). The cell pellet issolubilized in the chaotropic agent 6 Molar Guanidine HCl by stirringfor 3-4 hours at 4° C. The cell debris is removed by centrifugation, andthe supernatant containing the polypeptide is loaded onto anickel-nitrilo-tri-acetic acid (“Ni-NTA”) affinity resin column(available from QIAGEN, Inc., supra). Proteins with a 6×His tag bind tothe Ni-NTA resin with high affinity and can be purified in a simpleone-step procedure (for details see: The QlAexpressionist (1995) QIAGEN,Inc., supra).

[1050] Briefly, the supernatant is loaded onto the column in 6 Mguanidine-HCl, pH 8, the column is first washed with 10 volumes of 6 Mguanidine-HCl, pH 8, then washed with 10 volumes of 6 M guanidine-HCl pH6, and finally the polypeptide is eluted with 6 M guanidine-HCl, pH 5.

[1051] The purified protein is then renatured by dialyzing it againstphosphate-buffered saline (PBS) or 50 mM Na-acetate, pH 6 buffer plus200 mM NaCl. Alternatively, the protein can be successfully refoldedwhile immobilized on the Ni-NTA column. The recommended conditions areas follows: renature using a linear 6M-1M urea gradient in 500 mM NaCl,20% glycerol, 20 mM Tris/HCl pH 7.4, containing protease inhibitors. Therenaturation should be performed over a period of 1.5 hours or more.After renaturation the proteins are eluted by the addition of 250 mMimmidazole. Immidazole is removed by a final dialyzing step against PBSor 50 mM sodium acetate pH 6 buffer plus 200 mM NaCl. The purifiedprotein is stored at 4° C. or frozen at −80° C.

[1052] In addition to the above expression vector, the present inventionfurther includes an expression vector comprising phage operator andpromoter elements operatively linked to a polynucleotide of the presentinvention, called pHE4a. (ATCC Accession Number 209645, deposited onFeb. 25, 1998.) This vector contains: 1) a neomycinphosphotransferasegene as a selection marker, 2) an E. coli origin of replication, 3) a T5phage promoter sequence, 4) two lac operator sequences, 5) aShine-Delgarno sequence, and 6) the lactose operon repressor gene(lacIq). The origin of replication (oriC) is derived from pUC19 (LTI,Gaithersburg, Md.). The promoter sequence and operator sequences aremade synthetically.

[1053] DNA can be inserted into the pHEa by restricting the vector withNdeI and XbaI, BamHI, XhoI, or Asp718, running the restricted product ona gel, and isolating the larger fragment (the stuffer fragment should beabout 310 base pairs). The DNA insert is generated according to the PCRprotocol described in Example 1, using PCR primers having restrictionsites for NdeI (5′ primer) and XbaI, BamHI, XhoI, or Asp718 (3′ primer).The PCR insert is gel purified and restricted with compatible enzymes.The insert and vector are ligated according to standard protocols.

[1054] The engineered vector could easily be substituted in the aboveprotocol to express protein in a bacterial system.

Example 6 Purification of a Polypeptide from an Inclusion Body

[1055] The following alternative method can be used to purify apolypeptide expressed in E coli when it is present in the form ofinclusion bodies. Unless otherwise specified, all of the following stepsare conducted at 4-10° C.

[1056] Upon completion of the production phase of the E. colifermentation, the cell culture is cooled to 4-10° C. and the cellsharvested by continuous centrifugation at 15,000 rpm (Heraeus Sepatech).On the basis of the expected yield of protein per unit weight of cellpaste and the amount of purified protein required, an appropriate amountof cell paste, by weight, is suspended in a buffer solution containing100 mM Tris, 50 mM EDTA, pH 7.4. The cells are dispersed to ahomogeneous suspension using a high shear mixer.

[1057] The cells are then lysed by passing the solution through amicrofluidizer (Microfuidics, Corp. or APV Gaulin, Inc.) twice at4000-6000 psi. The homogenate is then mixed with NaCl solution to afinal concentration of 0.5 M NaCl, followed by centrifugation at 7000×gfor 15 min. The resultant pellet is washed again using 0.5M NaCl, 100 mMTris, 50 mM EDTA, pH 7.4.

[1058] The resulting washed inclusion bodies are solubilized with 1.5 Mguanidine hydrochloride (GuHCl) for 2-4 hours. After 7000×gcentrifugation for 15 min., the pellet is discarded and the polypeptidecontaining supernatant is incubated at 4° C. overnight to allow furtherGuHCl extraction.

[1059] Following high speed centrifugation (30,000×g) to removeinsoluble particles, the GuHCl solubilized protein is refolded byquickly mixing the GuHCl extract with 20 volumes of buffer containing 50mM sodium, pH 4.5, 150 mM NaCl, 2 mM EDTA by vigorous stirring. Therefolded diluted protein solution is kept at 4° C. without mixing for 12hours prior to further purification steps.

[1060] To clarify the refolded polypeptide solution, a previouslyprepared tangential filtration unit equipped with 0.16 μm membranefilter with appropriate surface area (e.g., Filtron), equilibrated with40 mM sodium acetate, pH 6.0 is employed. The filtered sample is loadedonto a cation exchange resin (e.g., Poros HS-50, Perseptive Biosystems).The column is washed with 40 mM sodium acetate, pH 6.0 and eluted with250 mM, 500 mM, 1000 mM, and 1500 mM NaCl in the same buffer, in astepwise manner. The absorbance at 280 nm of the effluent iscontinuously monitored. Fractions are collected and further analyzed bySDS-PAGE.

[1061] Fractions containing the polypeptide are then pooled and mixedwith 4 volumes of water. The diluted sample is then loaded onto apreviously prepared set of tandem columns of strong anion (Poros HQ-50,Perseptive Biosystems) and weak anion (Poros CM-20, PerseptiveBiosystems) exchange resins. The columns are equilibrated with 40 mMsodium acetate, pH 6.0. Both columns are washed with 40 mM sodiumacetate, pH 6.0, 200 mM NaCl. The CM-20 column is then eluted using a 10column volume linear gradient ranging from 0.2 M NaCl, 50 mM sodiumacetate, pH 6.0 to 1.0 M NaCl, 50 mM sodium acetate, pH 6.5. Fractionsare collected under constant A₂₈₀ monitoring of the effluent. Fractionscontaining the polypeptide (determined, for instance, by 16% SDS-PAGE)are then pooled.

[1062] The resultant polypeptide should exhibit greater than 95% purityafter the above refolding and purification steps. No major contaminantbands should be observed from Commassie blue stained 16% SDS-PAGE gelwhen 5 μg of purified protein is loaded. The purified protein can alsobe tested for endotoxin/LPS contamination, and typically the LPS contentis less than 0.1 ng/ml according to LAL assays.

Example 7 Cloning and Expression of a Polypeptide in a BaculovirusExpression System

[1063] In this example, the plasmid shuttle vector pA2 is used to inserta polynucleotide into a baculovirus to express a polypeptide. Thisexpression vector contains the strong polyhedrin promoter of theAutographa californica nuclear polyhedrosis virus (AcMNPV) followed byconvenient restriction sites such as BarnHI, Xba I and Asp718. Thepolyadenylation site of the simian virus 40 (“SV40”) is used forefficient polyadenylation. For easy selection of recombinant virus, theplasmid contains the beta-galactosidase gene from E. coli under controlof a weak Drosophila promoter in the same orientation, followed by thepolyadenylation signal of the polyhedrin gene. The inserted genes areflanked on both sides by viral sequences for cell-mediated homologousrecombination with wild-type viral DNA to generate a viable virus thatexpress the cloned polynucleotide.

[1064] Many other baculovirus vectors can be used in place of the vectorabove, such as pAc373, pVL941, and pAcIM1, as one skilled in the artwould readily appreciate, as long as the construct providesappropriately located signals for transcription, translation, secretionand the like, including a signal peptide and an in-frame AUG asrequired. Such vectors are described, for instance, in Luckow et al.,Virology 170:31-39 (1989).

[1065] Specifically, the cDNA sequence contained in the deposited clone,including the AUG initiation codon and the naturally associated leadersequence identified in Table 1, is amplified using the PCR protocoldescribed in Example 1. If the naturally occurring signal sequence isused to produce the secreted protein, the pA2 vector does not need asecond signal peptide. Alternatively, the vector can be modified (pA2GP) to include a baculovirus leader sequence, using the standard methodsdescribed in Summers et al., “A Manual of Methods for BaculovirusVectors and Insect Cell Culture Procedures,” Texas AgriculturalExperimental Station Bulletin No. 1555 (1987).

[1066] The amplified fragment is isolated from a 1% agarose gel using acommercially available kit (“Geneclean,” BIO 101 Inc., La Jolla,Calif.). The fragment then is digested with appropriate restrictionenzymes and again purified on a 1% agarose gel.

[1067] The plasmid is digested with the corresponding restrictionenzymes and optionally, can be dephosphorylated using calf intestinalphosphatase, using routine procedures known in the art. The DNA is thenisolated from a 1% agarose gel using a commercially available kit(“Geneclean” BIO 101 Inc., La Jolla, Calif.).

[1068] The fragment and the dephosphorylated plasmid are ligatedtogether with T4 DNA ligase. E. coli HB101 or other suitable E. colihosts such as XL-1 Blue (Stratagene Cloning Systems, La Jolla, Calif.)cells are transformed with the ligation mixture and spread on cultureplates. Bacteria containing the plasmid are identified by digesting DNAfrom individual colonies and analyzing the digestion product by gelelectrophoresis. The sequence of the cloned fragment is confirmed by DNAsequencing.

[1069] Five μg of a plasmid containing the polynucleotide isco-transfected with 1.0 μg of a commercially available linearizedbaculovirus DNA (“BaculoGold™ baculovirus DNA”, Pharmingen, San Diego,Calif.), using the lipofection method described by Felgner et al., Proc.Natl. Acad. Sci. USA 84:7413-7417 (1987). One μg of BaculoGold™ virusDNA and 5 μg of the plasmid are mixed in a sterile well of a microtiterplate containing 50 μl of serum-free Grace's medium (Life TechnologiesInc., Gaithersburg, Md.). Afterwards, 10 μl Lipofectin plus 90 μlGrace's medium are added, mixed and incubated for 15 minutes at roomtemperature. Then the transfection mixture is added drop-wise to Sf9insect cells (ATCC CRL 1711) seeded in a 35 mm tissue culture plate with1 ml Grace's medium without serum. The plate is then incubated for 5hours at 27° C. The transfection solution is then removed from the plateand 1 ml of Grace's insect medium supplemented with 10% fetal calf serumis added. Cultivation is then continued at 27° C. for four days.

[1070] After four days the supernatant is collected and a plaque assayis performed, as described by Summers and Smith, supra. An agarose gelwith “Blue Gal” (Life Technologies Inc., Gaithersburg) is used to alloweasy identification and isolation of gal-expressing clones, whichproduce blue-stained plaques. (A detailed description of a “plaqueassay” of this type can also be found in the user's guide for insectcell culture and baculovirology distributed by Life Technologies Inc.,Gaithersburg, page 9-10.) After appropriate incubation, blue stainedplaques are picked with the tip of a micropipettor (e.g., Eppendorf).The agar containing the recombinant viruses is then resuspended in amicrocentrifuge tube containing 200 μl of Grace's medium and thesuspension containing the recombinant baculovirus is used to infect Sf9cells seeded in 35 mm dishes. Four days later the supernatants of theseculture dishes are harvested and then they are stored at 4° C.

[1071] To verify the expression of the polypeptide, Sf9 cells are grownin Grace's medium supplemented with 10% heat-inactivated FBS. The cellsare infected with the recombinant baculovirus containing thepolynucleotide at a multiplicity of infection (“MOI”) of about 2. Ifradiolabeled proteins are desired, 6 hours later the medium is removedand is replaced with SF900 II medium minus methionine and cysteine(available from Life Technologies Inc., Rockville, Md.). After 42 hours,5 μCi of ³⁵S-methionine and 5 μCi ³⁵S-cysteine (available from Amersham)are added. The cells are further incubated for 16 hours and then areharvested by centrifugation. The proteins in the supernatant as well asthe intracellular proteins are analyzed by SDS-PAGE followed byautoradiography (if radiolabeled).

[1072] Microsequencing of the amino acid sequence of the arnino terminusof purified protein may be used to determine the amino terminal sequenceof the produced protein.

Example 8 Expression of a Polypeptide in Mammalian Cells

[1073] The polypeptide of the present invention can be expressed in amammalian cell. A typical mammalian expression vector contains apromoter element, which mediates the initiation of transcription ofmRNA, a protein coding sequence, and signals required for thetermination of transcription and polyadenylation of the transcript.Additional elements include enhancers, Kozak sequences and interveningsequences flanked by donor and acceptor sites for RNA splicing. Highlyefficient transcription is achieved with the early and late promotersfrom SV40, the long terminal repeats (LTRs) from Retroviruses, e.g.,RSV, HTLVI, HIVI and the early promoter of the cytomegalovirus (CMV).However, cellular elements can also be used (e.g., the human actinpromoter).

[1074] Suitable expression vectors for use in practicing the presentinvention include, for example, vectors such as pSVL and pMSG(Pharmacia, Uppsala, Sweden), pRSVcat (ATCC 37152), pSV2dhfr (ATCC37146), pBC12MI (ATCC 67109), pCMVSport 2.0, and pCMVSport 3.0.Mammalian host cells that could be used include, human Hela, 293, H9 andJurkat cells, mouse NIH3T3 and C127 cells, Cos 1, Cos 7 and CV1, quailQC1-3 cells, mouse L cells and Chinese hamster ovary (CHO) cells.

[1075] Alternatively, the polypeptide can be expressed in stable celllines containing the polynucleotide integrated into a chromosome. Theco-transfection with a selectable marker such as dhfr, gpt, neomycin,hygromycin allows the identification and isolation of the transfectedcells.

[1076] The transfected gene can also be amplified to express largeamounts of the encoded protein. The DHFR (dihydrofolate reductase)marker is useful in developing cell lines that carry several hundred oreven several thousand copies of the gene of interest. (See, e.g., Alt,F. W., et al., J. Biol. Chem. 253:1357-1370 (1978); Hamlin, J. L. andMa, C., Biochem. et Biophys. Acta, 1097:107-143 (1990); Page, M. J. andSydenham, M. A., Biotechnology 9:64-68 (1991).) Another useful selectionmarker is the enzyme glutamine synthase (GS) (Murphy et al., Biochem J.227:277-279 (1991); Bebbington et al., Bio/Technology 10:169-175 (1992).Using these markers, the mammalian cells are grown in selective mediumand the cells with the highest resistance are selected. These cell linescontain the amplified gene(s) integrated into a chromosome. Chinesehamster ovary (CHO) and NSO cells are often used for the production ofproteins.

[1077] Derivatives of the plasmid pSV2-dhfr (ATCC Accession No. 37146),the expression vectors pC4 (ATCC Accession No. 209646) and pC6 (ATCCAccession No.209647) contain the strong promoter (LTR) of the RousSarcoma Virus (Cullen et al., Molecular and Cellular Biology, 438-447(March, 1985)) plus a fragment of the CMV-enhancer (Boshart et al., Cell41:521-530 (1985).) Multiple cloning sites, e.g., with the restrictionenzyme cleavage sites BamHI, XbaI and Asp718, facilitate the cloning ofthe gene of interest. The vectors also contain the 3′ intron, thepolyadenylation and termination signal of the rat preproinsulin gene,and the mouse DHFR gene under control of the SV40 early promoter.

[1078] Specifically, the plasmid pC6, for example, is digested withappropriate restriction enzymes and then dephosphorylated using calfintestinal phosphates by procedures known in the art. The vector is thenisolated from a 1% agarose gel.

[1079] A polynucleotide of the present invention is amplified accordingto the protocol outlined in Example 1. If the naturally occurring signalsequence is used to produce the secreted protein, the vector does notneed a second signal peptide. Alternatively, if the naturally occurringsignal sequence is not used, the vector can be modified to include aheterologous signal sequence. (See, e.g., WO 96/34891.)

[1080] The amplified fragment is isolated from a 1% agarose gel using acommercially available kit (“Geneclean,” BIO 101 Inc., La Jolla,Calif.). The fragment then is digested with appropriate restrictionenzymes and again purified on a 1% agarose gel.

[1081] The amplified fragment is then digested with the same restrictionenzyme and purified on a 1% agarose gel. The isolated fragment and thedephosphorylated vector are then ligated with T4 DNA ligase. E. coli HB101 or XL-1 Blue cells are then transformed and bacteria are identifiedthat contain the fragment inserted into plasmid pC6 using, for instance,restriction enzyme analysis.

[1082] Chinese hamster ovary cells lacking an active DHFR gene is usedfor transfection. Five μg of the expression plasmid pC6 is cotransfectedwith 0.5 μg of the plasrmid pSVneo using lipofectin (Felgner et al.,supra). The plasmid pSV2-neo contains a dominant selectable marker, theneo gene from Tn5 encoding an enzyme that confers resistance to a groupof antibiotics including G418. The cells are seeded in alpha minus MEMsupplemented with 1 mg/ml G418. After 2 days, the cells are trypsinizedand seeded in hybridoma cloning plates (Greiner, Germany) in alpha minusMEM supplemented with 10, 25, or 50 ng/ml of metothrexate plus 1 mg/mlG418. After about 10-14 days single clones are trypsinized and thenseeded in 6-well petri dishes or 10 ml flasks using differentconcentrations of methotrexate (50 nM, 100 nM, 200 nM, 400 nM, 800 nM).Clones growing at the highest concentrations of methotrexate are thentransferred to new 6-well plates containing even higher concentrationsof methotrexate (1 μM, 2 μM, 5 μM, 10 mM, 20 mM). The same procedure isrepeated until clones are obtained which grow at a concentration of100-200 μM. Expression of the desired gene product is analyzed, forinstance, by SDS-PAGE and Western blot or by reversed phase HPLCanalysis.

Example 9 Protein Fusions

[1083] The polypeptides of the present invention are preferably fused toother proteins. These fusion proteins can be used for a variety ofapplications. For example, fusion of the present polypeptides toHis-tag, HA-tag, protein A, IgG domains, and maltose binding proteinfacilitates purification. (See Example 5; see also EP A 394,827;Traunecker, et al., Nature 331:84-86 (1988).) Similarly, fusion toIgG-1, IgG-3, and albumin increases the halflife time in vivo. Nuclearlocalization signals fused to the polypeptides of the present inventioncan target the protein to a specific subcellular localization, whilecovalent heterodimer or homodimers can increase or decrease the activityof a fusion protein. Fusion proteins can also create chimeric moleculeshaving more than one function. Finally, fusion proteins can increasesolubility and/or stability of the fused protein compared to thenon-fused protein. All of the types of fusion proteins described abovecan be made by modifying the following protocol, which outlines thefusion of a polypeptide to an IgG molecule, or the protocol described inExample 5.

[1084] Briefly, the human Fc portion of the IgG molecule can be PCRamplified, using primers that span the 5′ and 3′ ends of the sequencedescribed below. These primers also should have convenient restrictionenzyme sites that will facilitate cloning into an expression vectorpreferably a mammalian expression vector.

[1085] For example, if pC4 (Accession No. 209646) is used, the human Fcportion can be ligated into the BamHI cloning site. Note that the 3′BamHI site should be destroyed. Next, the vector containing the human Fcportion is re-restricted with BamHI, linearizing the vector, and apolynucleotide of the present invention, isolated by the PCR protocoldescribed in Example 1, is ligated into this BamHI site. Note that thepolynucleotide is cloned without a stop codon, otherwise a fusionprotein will not be produced.

[1086] If the naturally occurring signal sequence is used to produce thesecreted protein, pC4 does not need a second signal peptide.Alternatively, if the naturally occurring signal sequence is not used,the vector can be modified to include a heterologous signal sequence.(See, e.g., WO 96/34891.)

[1087] Human IgG Fc region: Human IgG Fc region:GGGATCCGGAGCCCAAATCTTCTGACAAAACTCACAC (SEQ ID NO:1)ATGCCCACCGTGCCCAGCACCTGAATTCGAGGGTGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACTCCTGAGGTCACATGCGTGGTGGTGGACGTAAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAACCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCAAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAA ATGAGTGCGACGGCCGCGACTCTAGAGGAT

Example 10 Production of an Antibody from a Polypeptide

[1088] The antibodies of the present invention can be prepared by avariety of methods. (See, Current Protocols, Chapter 2.) For example,cells expressing a polypeptide of the present invention is administeredto an animal to induce the production of sera containing polyclonalantibodies. In a preferred method, a preparation of the secreted proteinis prepared and purified to render it substantially free of naturalcontaminants. Such a preparation is then introduced into an animal inorder to produce polyclonal antisera of greater specific activity.

[1089] In the most preferred method, the antibodies of the presentinvention are monoclonal antibodies (or protein binding fragmentsthereof). Such monoclonal antibodies can be prepared using hybridomatechnology. (Köhler et al., Nature 256:495 (1975); Köhler et al., Eur.J. Immunol. 6:511 (1976); Köhler et al., Eur. J. Immunol. 6:292 (1976);Hammerling et al., in: Monoclonal Antibodies and T-Cell Hybridomas,Elsevier, N.Y., pp. 563-681 (1981).) In general, such procedures involveimmunizing an animal (preferably a mouse) with polypeptide or, morepreferably, with a secreted polypeptide-expressing cell. Such cells maybe cultured in any suitable tissue culture medium; however, it ispreferable to culture cells in Earle's modified Eagle's mediumsupplemented with 10% fetal bovine serum (inactivated at about 56° C.),and supplemented with about 10 g/l of nonessential amino acids, about1,000 U/ml of penicillin, and about 100 μg/ml of streptomycin.

[1090] The splenocytes of such mice are extracted and fused with asuitable myeloma cell line. Any suitable myeloma cell line may beemployed in accordance with the present invention; however, it ispreferable to employ the parent myeloma cell line (SP20), available fromthe ATCC. After fusion, the resulting hybridoma cells are selectivelymaintained in HAT medium, and then cloned by limiting dilution asdescribed by Wands et al. (Gastroenterology 80:225-232 (1981).) Thehybridoma cells obtained through such a selection are then assayed toidentify clones which secrete antibodies capable of binding thepolypeptide.

[1091] Alternatively, additional antibodies capable of binding to thepolypeptide can be produced in a two-step procedure using anti-idiotypicantibodies. Such a method makes use of the fact that antibodies arethemselves antigens, and therefore, it is possible to obtain an antibodywhich binds to a second antibody. In accordance with this method,protein specific antibodies are used to immunize an animal, preferably amouse. The splenocytes of such an animal are then used to producehybridoma cells, and the hybridoma cells are screened to identify cloneswhich produce an antibody whose ability to bind to the protein-specificantibody can be blocked by the polypeptide. Such antibodies compriseanti-idiotypic antibodies to the protein-specific antibody and can beused to immunize an animal to induce formation of furtherprotein-specific antibodies.

[1092] It will be appreciated that Fab and F(ab′)2 and other fragmentsof the antibodies of the present invention may be used according to themethods disclosed herein. Such fragments are typically produced byproteolytic cleavage, using enzymes such as papain (to produce Fabfragments) or pepsin (to produce F(ab′)2 fragments). Alternatively,secreted protein-binding fragments can be produced through theapplication of recombinant DNA technology or through syntheticchemistry.

[1093] For in vivo use of antibodies in humans, it may be preferable touse “humanized” chimeric monoclonal antibodies. Such antibodies can beproduced using genetic constructs derived from hybridoma cells producingthe monoclonal antibodies described above. Methods for producingchimeric antibodies are known in the art. (See, for review, Morrison,Science 229:1202 (1985); Oi et al., BioTechniques 4:214 (1986); Cabillyet al., U.S. Pat. No. 4,816,567; Taniguchi et al., EP 171496; Morrisonet al., EP 173494; Neuberger et al., WO 8601533; Robinson et al., WO8702671; Boulianne et al., Nature 312:643 (1984); Neubergeret al.,Nature 314:268 (1985).)

Example 11 Production of Secreted Protein for High-Throughput ScreeningAssays

[1094] The following protocol produces a supernatant containing apolypeptide to be tested. This supernatant can then be used in theScreening Assays described in Examples 13.-20.

[1095] First, dilute Poly-D-Lysine (644 587 Boehringer-Mannheim) stocksolution (1 mg/ml in PBS) 1:20 in PBS (w/o calcium or magnesium 17-516FBiowhittaker) for a working solution of 50 ug/ml. Add 200 ul of thissolution to each well (24 well plates) and incubate at RT for 20minutes. Be sure to distribute the solution over each well (note: a12-channel pipetter may be used with tips on every other channel).Aspirate off the Poly-D-Lysine solution and rinse with 1 ml PBS(Phosphate Buffered Saline). The PBS should remain in the well untiljust prior to plating the cells and plates may be poly-lysine coated inadvance for up to two weeks.

[1096] Plate 293T cells (do not carry cells past P+20) at 2×10⁵cells/well in 0.5 ml DMEM(Dulbecco's Modified Eagle Medium)(with 4.5 G/Lglucose and L-glutamine (12-604F Biowhittaker))/10% heat inactivatedFBS(14-503F Biowhittaker)/1×Penstrep(17-602E Biowhittaker). Let thecells grow overnight.

[1097] The next day, mix together in a sterile solution basin: 300 ulLipofectamine (18324-012 Gibco/BRL) and 5 ml Optimem I (31985070Gibco/BRL)/96-well plate. With a small volume multi-channel pipetter,aliquot approximately 2 ug of an expression vector containing apolynucleotide insert, produced by the methods described in Examples 8or 9, into an appropriately labeled 96-well round bottom plate. With amulti-channel pipetter, add 50 ul of the Lipofectamine/Optimem I mixtureto each well. Pipette up and down gently to mix. Incubate at RT 15-45minutes. After about 20 minutes, use a multi-channel pipetter to add 150ul Optimem I to each well. As a control, one plate of vector DNA lackingan insert should be transfected with each set of transfections.

[1098] Preferably, the transfection should be performed by tag-teamingthe following tasks. By tag-teaming, hands on time is cut in half, andthe cells do not spend too much time on PBS. First, person A aspiratesoff the media from four 24-well plates of cells, and then person Brinses each well with 0.5-1 ml PBS. Person A then aspirates off PBSrinse, and person B, using a12-channel pipetter with tips on every otherchannel, adds the 200 ul of DNA/Lipofectamine/Optimem I complex to theodd wells first, then to the even wells, to each row on the 24-wellplates. Incubate at 37° C. for 6 hours.

[1099] While cells are incubating, prepare appropriate media, either1%BSA in DMEM with 1×penstrep, or CHO-5 media (116.6 mg/L of CaCl2(anhyd); 0.00130 mg/L CuSO₄-5H₂O; 0.050 mg/L of Fe(NO₃)₃-9H₂O; 0.417mg/L of FeSO₄-7H₂O; 311.80 mg/L of Kcl; 28.64 mg/L of MgCl₂; 48.84 mg/Lof MgSO₄; 6995.50 mg/L of NaCl; 2400.0 mg/L of NaHCO₃; 62.50 mg/L ofNaH₂PO₄—H₂O; 71.02 mg/L of Na₂HPO4; 0.4320 mg/L of ZnSO₄-7H₂O; 0.002mg/L of Arachidonic Acid; 1.022 mg/L of Cholesterol; 0.070 mg/L ofDL-alpha-Tocopherol-Acetate; 0.0520 mg/L of Linoleic Acid; 0.010 mg/L ofLinolenic Acid; 0.010 mgl of Myristic Acid; 0.010 mg/L of Oleic Acid;0.010 mg/L of Palmitric Acid; 0.010 mg/L of Palmitic Acid; 100 mg/L ofPluronic F-68; 0.010 mg/L of Stearic Acid; 2.20 mg/L of Tween 80; 4551mg/L of D-Glucose; 130.85 mg/ml of L-Alanine; 147.50 mg/ml ofL-Arginine-HCL; 7.50 mg/ml of L-Asparagine-H₂O; 6.65 mg/ml of L-AsparticAcid; 29.56 mg/ml of L-Cystine-2HCL-H₂O; 31.29 mg/ml of L-Cystine-2HCL;7.35 mg/ml of L-Glutamic Acid; 365.0 mg/ml of L-Glutamine; 18.75 mg/mlof Glycine; 52.48 mg/ml of L-Histidine-HCL-H₂O; 106.97 mg/ml ofL-Isoleucine; 111.45 mg/ml of L-Leucine; 163.75 mg/ml of L-Lysine HCL;32.34 mg/ml of L-Methionine; 68.48 mg/ml of L-Phenylalainine; 40.0 mg/mlof L-Proline; 26.25 mg/ml of L-Serine; 101.05 mg/ml of L-Threonine;19.22 mg/ml of L-Tryptophan; 91.79 mg/ml of L-Tryrosine-2Na-2H₂O; 99.65mg/ml of L-Valine; 0.0035 mg/L of Biotin; 3.24 mg/L of D—CaPantothenate; 11.78 mg/L of Choline Chloride; 4.65 mg/L of Folic Acid;15.60 mg/L of i-Inositol; 3.02 mg/L of Niacinamide; 3.00 mg/L ofPyridoxal HCL; 0.031 mg/L of Pyridoxine HCL; 0.319 mg/L of Riboflavin;3.17 mg/L of Thiamine HCL; 0.365 mg/L of Thymidine; and 0.680 mg/L ofVitamin B₁₂; 25 mM of HEPES Buffer; 2.39 mg/L of Na Hypoxanthine; 0.105mg/L of Lipoic Acid; 0.081 mg/L of Sodium Putrescine-2HCL; 55.0 mg/L ofSodium Pyruvate; 0.0067 mg/L of Sodium Selenite; 20 uM of Ethanolamine;0.122 mg/L of Ferric Citrate; 41.70 mg/L of Methyl-B-Cyclodextrincomplexed with Linoleic Acid; 33.33 mg/L of Methyl-B-Cyclodextrincomplexed with Oleic Acid; and 10 mg/L of Methyl-B-Cyclodextrincomplexed with Retinal) with 2 mm glutamine and 1×penstrep. (BSA(81-068-3 Bayer) 100 gm dissolved in 1 L DMEM for a 10% BSA stocksolution). Filter the media and collect 50 ul for endotoxin assay in 15ml polystyrene conical.

[1100] The transfection reaction is terminated, preferably bytag-teaming, at the end of the incubation period. Person A aspirates offthe transfection media, while person B adds 1.5 ml appropriate media toeach well. Incubate at 37° C. for 45 or 72 hours depending on the mediaused: 1%BSA for 45 hours or CHO-5 for 72 hours.

[1101] On day four, using a 300 ul multichannel pipetter, aliquot 600 ulin one 1 ml deep well plate and the remaining supernatant into a 2 mldeep well. The supernatants from each well can then be used in theassays described in Examples 13-20.

[1102] It is specifically understood that when activity is obtained inany of the assays described below using a supernatant, the activityoriginates from either the polypeptide directly (e.g., as a secretedprotein) or by the polypeptide inducing expression of other proteins,which are then secreted into the supernatant. Thus, the inventionfurther provides a method of identifying the protein in the supernatantcharacterized by an activity in a particular assay.

Example 12 Construction of GAS Reporter Construct

[1103] One signal transduction pathway involved in the differentiationand proliferation of cells is called the Jaks-STATs pathway. Activatedproteins in the Jaks-STATs pathway bind to gamma activation site “GAS”elements or interferon-sensitive responsive element (“ISRE”), located inthe promoter of many genes. The binding of a protein to these elementsalter the expression of the associated gene.

[1104] GAS and ISRE elements are recognized by a class of transcriptionfactors called Signal Transducers and Activators of Transcription, or“STATs.” There are six members of the STATs family. Stat1 and Stat3 arepresent in many cell types, as is Stat2 (as response to IFN-alpha iswidespread). Stat4 is more restricted and is not in many cell typesthough it has been found in T helper class I, cells after treatment withIL-12. Stat5 was originally called mammary growth factor, but has beenfound at higher concentrations in other cells including myeloid cells.It can be activated in tissue culture cells by many cytokines.

[1105] The STATs are activated to translocate from the cytoplasm to thenucleus upon tyrosine phosphorylation by a set of kinases known as theJanus Kinase (“Jaks”) family. Jaks represent a distinct family ofsoluble tyrosine kinases and include Tyk2, Jak1, Jak2, and Jak3. Thesekinases display significant sequence similarity and are generallycatalytically inactive in resting cells.

[1106] The Jaks are activated by a wide range of receptors summarized inthe Table below. (Adapted from review by Schidler and Darnell, Ann. Rev.Biochem. 64:621-51 (1995).) A cytokine receptor family, capable ofactivating Jaks, is divided into two groups: (a) Class 1 includesreceptors for IL-2, IL-3, IL-4, IL-6, IL-7, IL-9, IL-11, IL-12, IL-15,Epo, PRL, GH, G-CSF, GM-CSF, LIF, CNTF, and thrombopoietin; and (b)Class 2 includes IFN-a, IFN-g, and IL-10. The Class 1 receptors share aconserved cysteine motif (a set of four conserved cysteines and onetryptophan) and a WSXWS motif (a membrane proximal region encodingTrp-Ser-Xxx-Trp-Ser (SEQ ID NO:2)).

[1107] Thus, on binding of a ligand to a receptor, Jaks are activated,which in turn activate STATs, which then translocate and bind to GASelements. This entire process is encompassed in the Jaks-STATs signaltransduction pathway.

[1108] Therefore, activation of the Jaks-STATs pathway, reflected by thebinding of the GAS or the ISRE element, can be used to indicate proteinsinvolved in the proliferation and differentiation of cells. For example,growth factors and cytokines are known to activate the Jaks-STATspathway. (See Table below.) Thus, by using GAS elements linked toreporter molecules, activators of the Jaks-STATs pathway can beidentified. JAKs Ligand tyk2 Jak1 Jak2 Jak3 STATS GAS (elements) or ISREIFN family IFN-a/B + + − − 1,2,3 ISRE IFN-g + + − 1 GAS (IRF1>Lys6>IFP)I1-10 + ? ? − 1,3 gp130 family IL-6 (Pleiotrophic) + + + ? 1,3 GAS(IRF1>Lys6>IFP) I1-11 (Pleiotrophic) ? + ? ? 1,3 OmM (Pleiotrophic)? + + ? 1,3 LIF (Pleiotrophic) ? + + ? 1,3 CNTF (Pleiotrophic) −/+ + + ?1,3 G-CSF (Pleiotrophic) ? + ? ? 1,3 IL-12 (Pleiotrophic) + − + + 1,3g-C family IL-2 (lymphocytes) − + − + 1,3,5 GAS IL-4 (lymph/myeloid) − +− + 6 GAS (IRF1 = IFP>>Ly6)(IgH) IL-7 (lymphocytes) − + − + 5 GAS IL-9(lymphocytes) − + − + 5 GAS IL-13 (lymphocyte) − + ? ? 6 GAS IL-15 ? +? + 5 GAS gp 140 family IL-3 (myeloid) − − + − 5 GAS (IRF1>IFP>>Ly6)IL-5 (myeloid) − − + − 5 GAS GM-CSF (myeloid) − − + − 5 GAS Growthhormone family GH ? − + − 5 GAS(B-CAS>IRF1 = IFP>>Ly6) PRL ? +/− + −1,3,5 EPO ? − + − 5 Receptor Tyrosine Kinases EGF ? + + − 1,3 GAS (IRF1)PDGF ? + + − 1,3 CSF-1 ? + + − 1,3 GAS (not IRF1)

[1109] To construct a synthetic GAS containing promoter element, whichis used in the Biological Assays described in Examples 13-14, a PCRbased strategy is employed to generate a GAS-SV40 promoter sequence. The5′ primer contains four tandem copies of the GAS binding site found inthe IRF1 promoter and previously demonstrated to bind STATs uponinduction with a range of cytokines (Rothman et al., Immunity 1:457-468(1994).), although other GAS or ISRE elements can be used instead. The5′ primer also contains 18 bp of sequence complementary to the SV40early promoter sequence and is flanked with an XhoI site. The sequenceof the 5′ primer is: 5′:GCGCCTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAG:3′(SEQ ID NO:3)

[1110] The downstream primer is complementary to the SV40 promoter andis flanked with a Hind III site: 5′:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3′ (SEQID NO:4)

[1111] PCR amplification is performed using the SV40 promoter templatepresent in the B-gal:promoter plasmid obtained from Clontech. Theresulting PCR fragment is digested with Xhol/Hind III and subcloned intoBLSK2-. (Stratagene.) Sequencing with forward and reverse primersconfirms that the insert contains the following sequence:5′:CTCGAGATTTCCCCGAAATCTAGATTTCCCCGAA (SEQ ID NO:5)ATGATTTCCCCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGC TTTTGCAAAAAGCTT:3′

[1112] With this GAS promoter element linked to the SV40 promoter, aGAS:SEAP2 reporter construct is next engineered. Here, the reportermolecule is a secreted alkaline phosphatase, or “SEAP.” Clearly,however, any reporter molecule can be instead of SEAP, in this or in anyof the other Examples. Well known reporter molecules that can be usedinstead of SEAP include chloramphenicol acetyltransferase (CAT),luciferase, alkaline phosphatase, B-galactosidase, green fluorescentprotein (GFP), or any protein detectable by an antibody.

[1113] The above sequence confirmed synthetic GAS-SV40 promoter elementis subcloned into the pSEAP-Promoter vector obtained from Clontech usingHindIII and XhoI, effectively replacing the SV40 promoter with theamplified GAS:SV40 promoter element, to create the GAS-SEAP vector.However, this vector does not contain a neomycin resistance gene, andtherefore, is not preferred for mammalian expression systems.

[1114] Thus, in order to generate mammalian stable cell lines expressingthe GAS-SEAP reporter, the GAS-SEAP cassette is removed from theGAS-SEAP vector using SalI and NotI, and inserted into a backbone vectorcontaining the neomycin resistance gene, such as pGFP-1 (Clontech),using these restriction sites in the multiple cloning site, to createthe GAS-SEAP/Neo vector. Once this vector is transfected into mammaliancells, this vector can then be used as a reporter molecule for GASbinding as described in Examples 13-14.

[1115] Other constructs can be made using the above description andreplacing GAS with a different promoter sequence. For example,construction of reporter molecules containing NFK-B and EGR promotersequences are described in Examples 15 and 16. However, many otherpromoters can be substituted using the protocols described in theseExamples. For instance, SRE, IL-2, NFAT, or Osteocalcin promoters can besubstituted, alone or in combination (e.g., GAS/NF-KB/EGR, GAS/NF-KB,I1-2/NFAT, or NF-KB/GAS). Similarly, other cell lines can be used totest reporter construct activity, such as HELA (epithelial), HUVEC(endothelial), Reh (B-cell), Saos-2 (osteoblast), HUVAC (aortic), orCardiomyocyte.

Example 13 High-Throughput Screening Assay for T-cell Activity

[1116] The following protocol is used to assess T-cell activity byidentifying factors, such as growth factors and cytokines, that mayproliferate or differentiate T-cells. T-cell activity is assessed usingthe GAS/SEAP/Neo construct produced in Example 12. Thus, factors thatincrease SEAP activity indicate the ability to activate the Jaks-STATSsignal transduction pathway. The T-cell used in this assay is JurkatT-cells (ATCC Accession No. TIB-152), although Molt-3 cells (ATCCAccession No. CRL-1552) and Molt-4 cells (ATCC Accession No. CRL-1582)cells can also be used.

[1117] Jurkat T-cells are lymphoblastic CD4+ Th1 helper cells. In orderto generate stable cell lines, approximately 2 million Jurkat cells aretransfected with the GAS-SEAP/neo vector using DMRIE-C (LifeTechnologies)(transfection procedure described below). The transfectedcells are seeded to a density of approximately 20,000 cells per well andtransfectants resistant to 1 mg/ml genticin selected. Resistant coloniesare expanded and then tested for their response to increasingconcentrations of interferon gamma. The dose response of a selectedclone is demonstrated.

[1118] Specifically, the following protocol will yield sufficient cellsfor 75 wells containing 200 ul of cells. Thus, it is either scaled up,or performed in multiple to generate sufficient cells for multiple 96well plates. Jurkat cells are maintained in RPMI+10% serum with1%Pen-Strep. Combine 2.5 mls of OPTI-MEM (Life Technologies) with 10 ugof plasmid DNA in a T25 flask. Add 2.5 ml OPTI-MEM containing 50 ul ofDMRIE-C and incubate at room temperature for 15-45 mins.

[1119] During the incubation period, count cell concentration, spin downthe required number of cells (10⁷ per transfection), and resuspend inOPTI-MEM to a final concentration of 10⁷ cells/ml. Then add 1 ml of1×10⁷ cells in OPTI-MEM to T25 flask and incubate at 37° C. for 6 hrs.After the incubation, add 10 ml of RPMI+15% serum.

[1120] The Jurkat:GAS-SEAP stable reporter lines are maintained inRPMI+10% serum, 1 mg/ml Genticin, and 1% Pen-Strep. These cells aretreated with supernatants containing a polypeptide as produced by theprotocol described in Example 11.

[1121] On the day of treatment with the supernatant, the cells should bewashed and resuspended in fresh RPMI+10% serum to a density of 500,000cells per ml. The exact number of cells required will depend on thenumber of supernatants being screened. For one 96 well plate,approximately 10 million cells (for 10 plates, 100 million cells) arerequired.

[1122] Transfer the cells to a triangular reservoir boat, in order todispense the cells into a 96 well dish, using a 12 channel pipette.Using a 12 channel pipette, transfer 200 ul of cells into each well(therefore adding 100,000 cells per well).

[1123] After all the plates have been seeded, 50 ul of the supernatantsare transferred directly from the 96 well plate containing thesupernatants into each well using a 12 channel pipette. In addition, adose of exogenous interferon gamma (0.1, 1.0, 10 ng) is added to wellsH9, H10, and H11 to serve as additional positive controls for the assay.

[1124] The 96 well dishes containing Jurkat cells treated withsupernatants are placed in an incubator for 48 hrs (note: this time isvariable between 48-72 hrs). 35 ul samples from each well are thentransferred to an opaque 96 well plate using a 12 channel pipette. Theopaque plates should be covered (using sellophene covers) and stored at−20° C. until SEAP assays are performed according to Example 17. Theplates containing the remaining treated cells are placed at 4° C. andserve as a source of material for repeating the assay on a specific wellif desired.

[1125] As a positive control, 100 Unit/ml interferon gamma can be usedwhich is known to activate Jurkat T cells. Over 30 fold induction istypically observed in the positive control wells.

[1126] The above protocol may be used in the generation of bothtransient, as well as, stable transfected cells, which would be apparentto those of skill in the art.

Example 14 High-Throughput Screening Assay Identifying Myeloid Activity

[1127] The following protocol is used to assess myeloid activity byidentifying factors, such as growth factors and cytokines, that mayproliferate or differentiate myeloid cells. Myeloid cell activity isassessed using the GAS/SEAP/Neo construct produced in Example 12. Thus,factors that increase SEAP activity indicate the ability to activate theJaks-STATS signal transduction pathway. The myeloid cell used in thisassay is U937, a pre-monocyte cell line, although TF-1, HL60, or KG1 canbe used.

[1128] To transiently transfect U937 cells with the GAS/SEAP/Neoconstruct produced in Example 12, a DEAE-Dextran method (Kharbanda et.al., 1994, Cell Growth & Differentiation, 5:259-265) is used. First,harvest 2×10e⁷ U937 cells and wash with PBS. The U937 cells are usuallygrown in RPMI 1640 medium containing 10% heat-inactivated fetal bovineserum (FBS) supplemented with 100 units/ml penicillin and 100 mg/mlstreptomycin.

[1129] Next, suspend the cells in 1 ml of 20 mM Tris-HCl (pH 7.4) buffercontaining 0.5 mg/ml DEAE-Dextran, 8 ug GAS-SEAP2 plasmid DNA, 140 mMNaCl, 5 mM KCl, 375 uM Na₂HPO₄.7H₂O, 1 mM MgCl₂, and 675 uM CaCl₂.Incubate at 37° C. for 45 min.

[1130] Wash the cells with RPMI 1640 medium containing 10% FBS and thenresuspend in 10 ml complete medium and incubate at 37° C. for 36 hr.

[1131] The GAS-SEAP/U937 stable cells are obtained by growing the cellsin 400 ug/ml G418. The G418-free medium is used for routine growth butevery one to two months, the cells should be re-grown in 400 ug/ml G418for couple of passages.

[1132] These cells are tested by harvesting 1×10⁸ cells (this is enoughfor ten 96-well plates assay) and wash with PBS. Suspend the cells in200 ml above described growth medium, with a final density of 5×10⁵cells/ml. Plate 200 ul cells per well in the 96-well plate (or 1×10⁵cells/well).

[1133] Add 50 ul of the supernatant prepared by the protocol describedin Example 11. Incubate at 37° C. for 48 to 72 hr. As a positivecontrol, 100 Unit/ml interferon gamma can be used which is known toactivate U937 cells. Over 30 fold induction is typically observed in thepositive control wells. SEAP assay the supernatant according to theprotocol described in Example 17.

Example 15 High-Throughput Screening Assay Identifying Neuronal Activity

[1134] When cells undergo differentiation and proliferation, a group ofgenes are activated through many different signal transduction pathways.One of these genes, EGR1 (early growth response gene 1), is induced invarious tissues and cell types upon activation. The promoter of EGR1 isresponsible for such induction. Using the EGR1 promoter linked toreporter molecules, activation of cells can be assessed.

[1135] Particularly, the following protocol is used to assess neuronalactivity in PC12 cell lines. PC12 cells (rat phenochromocytoma cells)are known to proliferate and/or differentiate by activation with anumber of mitogens, such as TPA (tetradecanoyl phorbol acetate), NGF(nerve growth factor), and EGF (epidermal growth factor). The EGR1 geneexpression is activated during this treatment. Thus, by stablytransfecting PC12 cells with a construct containing an EGR promoterlinked to SEAP reporter, activation of PC12 cells can be assessed.

[1136] The EGR/SEAP reporter construct can be assembled by the followingprotocol. The EGR-1 promoter sequence (−633 to +1)(Sakamoto K et al.,Oncogene 6:867-871 (1991)) can be PCR amplified from human genomic DNAusing the following primers:

[1137] 5′ GCGCTCGAGGGATGACAGCGATAGAACCCCGG-3′ (SEQ ID NO:6)

[1138] 5′ GCGAAGCTTCGCGACTCCCCGGATCCGCCTC-3′ (SEQ ID NO:7)

[1139] Using the GAS:SEAP/Neo vector produced in Example 12, EGR1amplified product can then be inserted into this vector. Linearize theGAS:SEAP/Neo vector using restriction enzymes XhoI/HindIII, removing theGAS/SV40 stuffer. Restrict the EGR1 amplified product with these sameenzymes. Ligate the vector and the EGR1 promoter.

[1140] To prepare 96 well-plates for cell culture, two mls of a coatingsolution (1:30 dilution of collagen type I (Upstate Biotech Inc.Cat#08-115) in 30% ethanol (filter sterilized)) is added per one 10 cmplate or 50 ml per well of the 96-well plate, and allowed to air dry for2 hr.

[1141] PC12 cells are routinely grown in RPMI-1640 medium (BioWhittaker) containing 10% horse serum (JRH BIOSCIENCES, Cat. #12449-78P), 5% heat-inactivated fetal bovine serum (FBS) supplementedwith 100 units/ml penicillin and 100 ug/ml streptomycin on a precoated10 cm tissue culture dish. One to four split is done every three to fourdays. Cells are removed from the plates by scraping and resuspended withpipetting up and down for more than 15 times.

[1142] Transfect the EGR/SEAP/Neo construct into PC12 using theLipofectamine protocol described in Example 11. EGR-SEAP/PC12 stablecells are obtained by growing the cells in 300 ug/ml G418. The G418-freemedium is used for routine growth but every one to two months, the cellsshould be re-grown in 300 ug/ml G418 for couple of passages.

[1143] To assay forneuronal activity, a 10 cm plate with cells around 70to 80% confluent is screened by removing the old medium. Wash the cellsonce with PBS (Phosphate buffered saline). Then starve the cells in lowserum medium (RPMI-1640 containing 1% horse serum and 0.5% FBS withantibiotics) overnight.

[1144] The next morning, remove the medium and wash the cells with PBS.Scrape off the cells from the plate, suspend the cells well in 2 ml lowserum medium. Count the cell number and add more low serum medium toreach final cell density as 5×10⁵ cells/ml.

[1145] Add 200 ul of the cell suspension to each well of 96-well plate(equivalent to 1×10⁵ cells/well). Add 50 ul supernatant produced byExample 11, 37° C. for 48 to 72 hr. As a positive control, a growthfactor known to activate PC12 cells through EGR can be used, such as 50ng/ul of Neuronal Growth Factor (NGF). Over fifty-fold induction of SEAPis typically seen in the positive control wells. SEAP assay thesupernatant according to Example 17.

Example 16 High-Throughput Screening Assay for T-cell Activity

[1146] NF-κB (Nuclear Factor κB) is a transcription factor activated bya wide variety of agents including the inflammatory cytokines IL-1 andTNF, CD30 and CD40, lymphotoxin-alpha and lymphotoxin-beta, by exposureto LPS or thrombin, and by expression of certain viral gene products. Asa transcription factor, NF-κB regulates the expression of genes involvedin immune cell activation, control of apoptosis (NF-κB appears to shieldcells from apoptosis), B and T-cell development, anti-viral andantimicrobial responses, and multiple stress responses.

[1147] In non-stimulated conditions, NF-κB is retained in the cytoplasmwith I-κB (Inhibitor κB). However, upon stimulation, I-κB isphosphorylated and degraded, causing NF-κB to shuttle to the nucleus,thereby activating transcription of target genes. Target genes activatedby NF-κB include IL-2, IL-6, GM-CSF, ICAM-1 and class 1 MHC.

[1148] Due to its central role and ability to respond to a range ofstimuli, reporter constructs utilizing the NF-κB promoter element areused to screen the supernatants produced in Example 11. Activators orinhibitors of NF-κB would be useful in treating diseases. For example,inhibitors of NF-κB could be used to treat those diseases related to theacute or chronic activation of NF-κB, such as rheumatoid arthritis.

[1149] To construct a vector containing the NF-κB promoter element, aPCR based strategy is employed. The upstream primer contains four tandemcopies of the NF-κB binding site (GGGGACTTTCCC) (SEQ ID NO:8), 18 bp ofsequence complementary to the 5′ end of the SV40 early promotersequence, and is flanked with an XhoI site:5′:GCGGCCTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGACTTTCCATCCTGCCATCTCAATTAG:3′(SEQ ID NO:9)

[1150] The downstream primer is complementary to the 3′ end of the SV40promoter and is flanked with a Hind III site: 5′:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3′ (SEQ ID NO:4)

[1151] PCR amplification is performed using the SV40 promoter templatepresent in the pB-gal:promoter plasmid obtained from Clontech. Theresulting PCR fragment is digested with XhoI and Hind III and subclonedinto BLSK2-. (Stratagene) Sequencing with the T7 and T3 primers confirmsthe insert contains the following sequence:5′:CTCGAGGGGACTTTCCCGGGGACTTTCCGGGGA (SEQ ID NO:10)CTTTCCGGGACTTTCCATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAA AAAGCTT:3′

[1152] Next, replace the SV40 minimal promoter element present in thepSEAP2-promoter plasmid (Clontech) with this NF-κB/SV40 fragment usingXhoI and HindIII. However, this vector does not contain a neomycinresistance gene, and therefore, is not preferred for mammalianexpression systems.

[1153] In order to generate stable mammalian cell lines, theNF-κB/SV40/SEAP cassette is removed from the above NF-κB/SEAP vectorusing restriction enzymes SaI and NotI, and inserted into a vectorcontaining neomycin resistance. Particularly, the NF-κB/SV40/SEAPcassette was inserted into pGFP-1 (Clontech), replacing the GFP gene,after restricting pGFP-1 with SalI and NotI.

[1154] Once NF-κB/SV40/SEAP/Neo vector is created, stable Jurkat T-cellsare created and maintained according to the protocol described inExample 13. Similarly, the method for assaying supernatants with thesestable Jurkat T-cells is also described in example 13. As a positivecontrol, exogenous TNF alpha (0.1,1, 10 ng) is added to wells H9, H10,and H11, with a 5-10 fold activation typically observed.

Example 17 Assay for SEAP Activity

[1155] As a reporter molecule for the assays described in Examples13-16, SEAP activity is assayed using the Tropix Phospho-light Kit (Cat.BP-400) according to the following general procedure. The TropixPhospho-light Kit supplies the Dilution, Assay, and Reaction Buffersused below.

[1156] Prime a dispenser with the 2.5×Dilution Buffer and dispense 15 μlof 2.5×dilution buffer into Optiplates containing 35 μl of asupernatant. Seal the plates with a plastic sealer and incubate at 65°C. for 30 min. Separate the Optiplates to avoid uneven heating.

[1157] Cool the samples to room temperature for 15 minutes. Empty thedispenser and prime with the Assay Buffer. Add 50 μl Assay Buffer andincubate at room temperature 5 min. Empty the dispenser and prime withthe Reaction Buffer (see the table below). Add 50 μl Reaction Buffer andincubate at room temperature for 20 minutes. Since the intensity of thechemiluminescent signal is time dependent, and it takes about 10 minutesto read 5 plates on luminometer, one should treat 5 plates at each timeand start the second set 10 minutes later.

[1158] Read the relative light unit in the luminometer. Set H12 asblank, and print the results. An increase in chemiluminescence indicatesreporter activity. Reaction Buffer Formulation: # of plates Rxn bufferdiluent (ml) CSPD (ml) 10 60 3 11 65 3.25 12 70 3.5 13 75 3.75 14 80 415 85 4.25 16 90 4.5 17 95 4.75 18 100 5 19 105 5.25 20 110 5.5 21 1155.75 22 120 6 23 125 6.25 24 130 6.5 25 135 6.75 26 140 7 27 145 7.25 28150 7.5 29 155 7.75 30 160 8 31 165 8.25 32 170 8.5 33 175 8.75 34 180 935 185 9.25 36 190 9.5 37 195 9.75 38 200 10 39 205 10.25 40 210 10.5 41215 10.75 42 220 11 43 225 11.25 44 230 11.5 45 235 11.75 46 240 12 47245 12.25 48 250 12.5 49 255 12.75 50 260 13

Example 18 High-Throughput Screening Assay Identifying Changes in SmallMolecule Concentration and Membrane Permeability

[1159] Binding of a ligand to a receptor is known to alter intracellularlevels of small molecules, such as calcium, potassium, sodium, and pH,as well as alter membrane potential. These alterations can be measuredin an assay to identify supernatants which bind to receptors of aparticular cell. Although the following protocol describes an assay forcalcium, this protocol can easily be modified to detect changes inpotassium, sodium, pH, membrane potential, or any other small moleculewhich is detectable by a fluorescent probe.

[1160] The following assay uses Fluorometric Imaging Plate Reader(“FLIPR”) to measure changes in fluorescent molecules (Molecular Probes)that bind small molecules. Clearly, any fluorescent molecule detecting asmall molecule can be used instead of the calcium fluorescent molecule,fluo-4 (Molecular Probes, Inc.; catalog no. F-14202),used here.

[1161] For adherent cells, seed the cells at 10,000-20,000 cells/well ina Co-star black 96-well plate with clear bottom. The plate is incubatedin a CO₂ incubator for 20 hours. The adherent cells are washed two timesin Biotek washer with 200 ul of HBSS (Hank's Balanced Salt Solution)leaving 100 ul of buffer after the final wash.

[1162] A stock solution of 1 mg/ml fluo-4 is made in 10% pluronic acidDMSO. To load the cells with fluo-4, 50 ul of 12 ug/ml fluo-4 is addedto each well. The plate is incubated at 37° C. in a CO₂ incubator for 60min. The plate is washed four times in the Biotek washer with HBSSleaving 100 ul of buffer.

[1163] For non-adherent cells, the cells are spun down from culturemedia. Cells are re-suspended to 2-5×10⁶ cells/ml with HBSS in a 50-mlconical tube. 4 ul of 1 mg/ml fluo-4 solution in 10% pluronic acid DMSOis added to each ml of cell suspension. The tube is then placed in a 37°C. water bath for 30-60 min. The cells are washed twice with HBSS,resuspended to 1×10⁶ cells/ml, and dispensed into a microplate, 100ul/well. The plate is centrifuged at 1000 rpm for 5 min. The plate isthen washed once in Denley CellWash with 200 ul, followed by anaspiration step to 100 ul final volume.

[1164] For a non-cell based assay, each well contains a fluorescentmolecule, such as fluo-4. The supernatant is added to the well, and achange in fluorescence is detected.

[1165] To measure the fluorescence of intracellular calcium, the FLIPRis set for the following parameters: (1) System gain is 300-800 mW; (2)Exposure time is 0.4 second; (3) Camera F/stop is F/2; (4) Excitation is488 nm; (5) Emission is 530 nm; and (6) Sample addition is 50 ul.Increased emission at 530 nm indicates an extracellular signaling eventwhich has resulted in an increase in the intracellular Ca⁺⁺concentration.

Example 19 High-Throughput Screening Assay Identifying Tyrosine KinaseActivity

[1166] The Protein Tyrosine Kinases (PTK) represent a diverse group oftransmembrane and cytoplasmic kinases. Within the Receptor ProteinTyrosine Kinase RPTK) group are receptors for a range of mitogenic andmetabolic growth factors including the PDGF, FGF, EGF, NGF, HGF andInsulin receptor subfamilies. In addition there are a large family ofRPTKs for which the corresponding ligand is unknown. Ligands for RPTKsinclude mainly secreted small proteins, but also membrane-bound andextracellular matrix proteins.

[1167] Activation of RPTK by ligands involves ligand-mediated receptordimerization, resulting in transphosphorylation of the receptor subunitsand activation of the cytoplasmic tyrosine kinases. The cytoplasmictyrosine kinases include receptor associated tyrosine kinases of thesrc-family (e.g., src, yes, lck, lyn, fyn) and non-receptor linked andcytosolic protein tyrosine kinases, such as the Jak family, members ofwhich mediate signal transduction triggered by the cytokine superfamilyof receptors (e.g., the Interleukins, Interferons, GM-CSF, and Leptin).

[1168] Because of the wide range of known factors capable of stimulatingtyrosine kinase activity, the identification of novel human secretedproteins capable of activating tyrosine kinase signal transductionpathways are of interest. Therefore, the following protocol is designedto identify those novel human secreted proteins capable of activatingthe tyrosine kinase signal transduction pathways.

[1169] Seed target cells (e.g., primary keratinocytes) at a density ofapproximately 25,000 cells per well in a 96 well Loprodyne Silent ScreenPlates purchased from Nalge Nunc (Naperville, Ill.). The plates aresterilized with two 30 minute rinses with 100% ethanol, rinsed withwater and dried overnight. Some plates are coated for 2 hr with 100 mlof cell culture grade type I collagen (50 mg/ml), gelatin (2%) orpolylysine (50 mg/ml), all of which can be purchased from SigmaChemicals (St. Louis, Mo.) or 10% Matrigel purchased from BectonDickinson (Bedford, Mass.), or calf serum, rinsed with PBS and stored at4° C. Cell growth on these plates is assayed by seeding 5,000 cells/wellin growth medium and indirect quantitation of cell number through use ofalamarBlue as described by the manufacturer Alamar Biosciences, Inc.(Sacramento, Calif.) after 48 hr. Falcon plate covers #3071 from BectonDickinson (Bedford, Mass.) are used to cover the Loprodyne Silent ScreenPlates. Falcon Microtest III cell culture plates can also be used insome proliferation experiments.

[1170] To prepare extracts, A431 cells are seeded onto the nylonmembranes of Loprodyne plates (20,000/200 ml/well) and culturedovernight in complete medium. Cells are quiesced by incubation inserum-free basal medium for 24 hr. After 520 minutes treatment with EGF(60 ng/ml) or 50 ul of the supernatant produced in Example 11, themedium was removed and 100 ml of extraction buffer ((20 MM HEPES pH 7.5,0.15 M NaCl, 1% Triton X-100, 0.1% SDS, 2 mM Na3VO4, 2 mM Na4P2O7 and acocktail of protease inhibitors (# 1836170) obtained from BoeheringerMannheim (Indianapolis, Ind.) is added to each well and the plate isshaken on a rotating shaker for 5 minutes at 4° C. The plate is thenplaced in a vacuum transfer manifold and the extract filtered throughthe 0.45 mm membrane bottoms of each well using house vacuum. Extractsare collected in a 96-well catch/assay plate in the bottom of the vacuummanifold and immediately placed on ice. To obtain extracts clarified bycentrifugation, the content of each well, after detergent solubilizationfor 5 minutes, is removed and centrifuged for 15 minutes at 4° C. at16,000×g.

[1171] Test the filtered extracts for levels of tyrosine kinaseactivity. Although many methods of detecting tyrosine kinase activityare known, one method is described here.

[1172] Generally, the tyrosine kinase activity of a supernatant isevaluated by determining its ability to phosphorylate a tyrosine residueon a specific substrate (a biotinylated peptide). Biotinylated peptidesthat can be used for this purpose include PSK1 (corresponding to aminoacids 6-20 of the cell division kinase cdc2-p34) and PSK2 (correspondingto amino acids 1-17 of gastrin). Both peptides are substrates for arange of tyrosine kinases and are available from Boehringer Mannheim.

[1173] The tyrosine kinase reaction is set up by adding the followingcomponents in order. First, add 10 ul of 5 uM Biotinylated Peptide, then10 ul ATP/Mg₂₊ (5 mM ATP/50 mM MgCl₂), then 10 ul of 5×Assay Buffer (40mM imidazole hydrochloride, pH7.3, 40 mM beta-glycerophosphate, 1 mMEGTA, 100 mM MgCl₂, 5 mM MnCl₂, 0.5 mg/ml BSA), then 5 ul of SodiumVanadate(1 mM), and then 5 ul of water. Mix the components gently andpreincubate the reaction mix at 30° C. for 2 min. Initial the reactionby adding 10 ul of the control enzyme or the filtered supernatant.

[1174] The tyrosine kinase assay reaction is then terminated by adding10 ul of 120 mm EDTA and place the reactions on ice.

[1175] Tyrosine kinase activity is determined by transferring 50 ulaliquot of reaction mixture to a microtiter plate (MTP) module andincubating at 37° C. for 20 min. This allows the streptavadin coated 96well plate to associate with the biotinylated peptide. Wash the MTPmodule with 300 ul/well of PBS four times. Next add 75 ul ofanti-phospotyrosine antibody conjugated to horse radishperoxidase(anti-P-Tyr-POD(0.5 u/ml)) to each well and incubate at 37° C.for one hour. Wash the well as above.

[1176] Next add 100 ul of peroxidase substrate solution (BoehringerMannheim) and incubate at room temperature for at least 5 mins (up to 30min). Measure the absorbance of the sample at 405 nm by using ELISAreader. The level of bound peroxidase activity is quantitated using anELISA reader and reflects the level of tyrosine kinase activity.

Example 20 High-Throughput Screening Assay Identifying PhosphorylationActivity

[1177] As a potential alternative and/or compliment to the assay ofprotein tyrosine kinase activity described in Example 19, an assay whichdetects activation (phosphorylation) of major intracellular signaltransduction intermediates can also be used. For example, as describedbelow one particular assay can detect tyrosine phosphorylation of theErk-1 and Erk-2 kinases. However, phosphorylation of other molecules,such as Raf, JNK, p38 MAP, Map kinase kinase (MEK), MEK kinase, Src,Muscle specific kinase (MuSK), IRAK, Tec, and Janus, as well as anyother phosphoserine, phosphotyrosine, or phosphothreonine molecule, canbe detected by substituting these molecules for Erk-1 or Erk-2 in thefollowing assay.

[1178] Specifically, assay plates are made by coating the wells of a96-well ELISA plate with 0.1 ml of protein G (1 ug/ml) for 2 hr at roomtemp, (RT). The plates are then rinsed with PBS and blocked with 3%BSA/PBS for 1 hr at RT. The protein G plates are then treated with 2commercial monoclonal antibodies (100 ng/well) against Erk-1 and Erk-2(1 hr at RT) (Santa Cruz Biotechnology). (To detect other molecules,this step can easily be modified by substituting a monoclonal antibodydetecting any of the above described molecules.) After 3-5 rinses withPBS, the plates are stored at 4° C. until use.

[1179] A431 cells are seeded at 20,000/well in a 96-well Loprodynefilterplate and cultured overnight in growth medium. The cells are thenstarved for 48 hr in basal medium (DMEM) and then treated with EGF (6ng/well) or 50 ul of the supernatants obtained in Example 11 for 5-20minutes. The cells are then solubilized and extracts filtered directlyinto the assay plate.

[1180] After incubation with the extract for 1 hr at RT, the wells areagain rinsed. As a positive control, a commercial preparation of MAPkinase (10 ng/well) is used in place of A431 extract. Plates are thentreated with a commercial polyclonal (rabbit) antibody (1lug/mi) whichspecifically recognizes the phosphorylated epitope of the Erk-1 andErk-2 kinases (1 hr at RT). This antibody is biotinylated by standardprocedures. The bound polyclonal antibody is then quantitated bysuccessive incubations with Europium-streptavidin and Europiumfluorescence enhancing reagent in the Wallac DELFIA instrument(time-resolved fluorescence). An increased fluorescent signal overbackground indicates a phosphorylation.

Example 21 Method of Determining Alterations in a Gene Corresponding toa Polynucleotide

[1181] RNA isolated from entire families or individual patientspresenting with a phenotype of interest (such as a disease) is beisolated. cDNA is then generated from these RNA samples using protocolsknown in the art. (See, Sambrook.) The cDNA is then used as a templatefor PCR, employing primers surrounding regions of interest in SEQ IDNO:X. Suggested PCR conditions consist of 35 cycles at 95° C. for 30seconds; 60-120 seconds at 52-58° C.; and 60-120 seconds at 70° C.,using buffer solutions described in Sidransky, D., et al., Science252:706 (1991).

[1182] PCR products are then sequenced using primers labeled at their 5′end with T4 polynucleotide kinase, employing SequiTherm Polymerase.(Epicentre Technologies). The intron-exon borders of selected exons isalso determined and genomic PCR products analyzed to confirm theresults. PCR products harboring suspected mutations is then cloned andsequenced to validate the results of the direct sequencing.

[1183] PCR products is cloned into T-tailed vectors as described inHolton, T. A. and Graham, M. W., Nucleic Acids Research, 19:1156 (1991)and sequenced with T7 polymerase (United States Biochemical). Affectedindividuals are identified by mutations not present in unaffectedindividuals.

[1184] Genormic rearrangements are also observed as a method ofdetermining alterations in a gene corresponding to a polynucleotide.Genomic clones isolated according to Example 2 are nick-translated withdigoxigenindeoxy-uridine 5′-triphosphate (Boehringer Manheim), and FISHperformed as described in Johnson, Cg. et al., Methods Cell Biol.35:73-99 (1991). Hybridization with the labeled probe is carried outusing a vast excess of human cot-1 DNA for specific hybridization to thecorresponding genomic locus.

[1185] Chromosomes are counterstained with 4,6-diamino-2-phenylidole andpropidium iodide, producing a combination of C- and R-bands. Alignedimages for precise mapping are obtained using a triple-band filter set(Chroma Technology, Brattleboro, Vt.) in combination with a cooledcharge-coupled device camera (Photometrics, Tucson, Ariz.) and variableexcitation wavelength filters. (Johnson, Cv. et al., Genet. Anal. Tech.Appl., 8:75 (1991).) Image collection, analysis and chromosomalfractional length measurements are performed using the ISee GraphicalProgram System. (Inovision Corporation, Durham, N.C.) Chromosomealterations of the genomic region hybridized by the probe are identifiedas insertions, deletions, and translocations. These alterations are usedas a diagnostic marker for an associated disease.

Example 22 Method of Detecting Abnormal Levels of a Polypeptide in aBiological Sample

[1186] A polypeptide of the present invention can be detected in abiological sample, and if an increased or decreased level of thepolypeptide is detected, this polypeptide is a marker for a particularphenotype. Methods of detection are numerous, and thus, it is understoodthat one skilled in the art can modify the following assay to fit theirparticular needs.

[1187] For example, antibody-sandwich ELISAs are used to detectpolypeptides in a sample, preferably a biological sample. Wells of amicrotiter plate are coated with specific antibodies, at a finalconcentration of 0.2 to 10 ug/ml. The antibodies are either monoclonalor polyclonal and are produced by the method described in Example 10.The wells are blocked so that non-specific binding of the polypeptide tothe well is reduced.

[1188] The coated wells are then incubated for >2 hours at RT with asample containing the polypeptide. Preferably, serial dilutions of thesample should be used to validate results. The plates are then washedthree times with deionized or distilled water to remove unboundedpolypeptide.

[1189] Next, 50 ul of specific antibody-alkaline phosphatase conjugate,at a concentration of 25-400 ng, is added and incubated for 2 hours atroom temperature. The plates are again washed three times with deionizedor distilled water to remove unbounded conjugate.

[1190] Add 75 ul of 4-methylumbelliferyl phosphate (MUP) orp-nitrophenyl phosphate (NPP) substrate solution to each well andincubate 1 hour at room temperature. Measure the reaction by amicrotiter plate reader. Prepare a standard curve, using serialdilutions of a control sample, and plot polypeptide concentration on theX-axis (log scale) and fluorescence or absorbance of the Y-axis (linearscale). Interpolate the concentration of the polypeptide in the sampleusing the standard curve.

Example 23 Formulating a Polypeptide

[1191] The secreted polypeptide composition will be formulated and dosedin a fashion consistent with good medical practice, taking into accountthe clinical condition of the individual patient (especially the sideeffects of treatment with the secreted polypeptide alone), the site ofdelivery, the method of administration, the scheduling ofadministration, and other factors known to practitioners. The “effectiveamount” for purposes herein is thus determined by such considerations.

[1192] As a general proposition, the total pharmaceutically effectiveamount of secreted polypeptide administered parenterally per dose willbe in the range of about 1 μg/kg/day to 10 mg/kg/day of patient bodyweight, although, as noted above, this will be subject to therapeuticdiscretion. More preferably, this dose is at least 0.01 mg/kg/day, andmost preferably for humans between about 0.01 and 1 mg/kg/day for thehormone. If given continuously, the secreted polypeptide is typicallyadministered at a dose rate of about 1 μg/kg/hour to about 50μg/kg/hour, either by 1-4 injections per day or by continuoussubcutaneous infusions, for example, using a mini-pump. An intravenousbag solution may also be employed. The length of treatment needed toobserve changes and the interval following treatment for responses tooccur appears to vary depending on the desired effect.

[1193] Pharmaceutical compositions containing the secreted protein ofthe invention are administered orally, rectally, parenterally,intracistemally, intravaginally, intraperitoneally, topically (as bypowders, ointments, gels, drops or transdermal patch), bucally, or as anoral or nasal spray. “Pharmaceutically acceptable carrier” refers to anon-toxic solid, semisolid or liquid filler, diluent, encapsulatingmaterial or formulation auxiliary of any type. The term “parenteral” asused herein refers to modes of administration which include intravenous,intramuscular, intraperitoneal, intrastemal, subcutaneous andintraarticular injection and infusion.

[1194] The secreted polypeptide is also suitably administered bysustained-release systems. Suitable examples of sustained-releasecompositions include semi-permeable polymer matrices in the form ofshaped articles, e.g., films, or mirocapsules. Sustained-releasematrices include polylactides (U.S. Pat. No. 3,773,919, EP 58,481),copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman, U. etal., Biopolymers 22:547-556 (1983)), poly (2-hydroxyethyl methacrylate)(R. Langer et al., J. Biomed. Mater. Res. 15:167-277 (1981), and R.Langer, Chem. Tech. 12:98-105 (1982)), ethylene vinyl acetate (R. Langeret al.) or poly-D-(−)-3-hydroxybutyric acid (EP 133,988).Sustained-release compositions also include liposomally entrappedpolypeptides. Liposomes containing the secreted polypeptide are preparedby methods known per se: DE 3,218,121; Epstein et al., Proc. Natl. Acad.Sci. USA 82:3688-3692 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA77:4030-4034 (1980); EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP142,641; Japanese Pat. Appl. 83-118008; U.S. Pat. Nos. 4,485,045 and4,544,545; and EP 102,324. Ordinarily, the liposomes are of the small(about 200-800 Angstroms) unilamellar type in which the lipid content isgreater than about 30 mol. percent cholesterol, the selected proportionbeing adjusted for the optimal secreted polypeptide therapy.

[1195] For parenteral administration, in one embodiment, the secretedpolypeptide is formulated generally by mixing it at the desired degreeof purity, in a unit dosage injectable form (solution, suspension, oremulsion), with a pharmaceutically acceptable carrier, i.e., one that isnon-toxic to recipients at the dosages and concentrations employed andis compatible with other ingredients of the formulation. For example,the formulation preferably does not include oxidizing agents and othercompounds that are known to be deleterious to polypeptides.

[1196] Generally, the formulations are prepared by contacting thepolypeptide uniformly and intimately with liquid carriers or finelydivided solid carriers or both. Then. if necessary, the product isshaped into the desired formulation. Preferably the carrier is aparenteral carrier, more preferably a solution that is isotonic with theblood of the recipient. Examples of such carrier vehicles include water,saline, Ringer's solution, and dextrose solution. Non-aqueous vehiclessuch as fixed oils and ethyl oleate are also useful herein, as well asliposomes.

[1197] The carrier suitably contains minor amounts of additives such assubstances that enhance isotonicity and chemical stability. Suchmaterials are non-toxic to recipients at the dosages and concentrationsemployed, and include buffers such as phosphate, citrate, succinate,acetic acid, and other organic acids or their salts; antioxidants suchas ascorbic acid; low molecular weight (less than about ten residues)polypeptides, e.g., polyarginine or tripeptides; proteins, such as serumalbumin, gelatin, or immunoglobulins; hydrophilic polymers such aspolyvinylpyrrolidone; amino acids, such as glycine, glutamic acid,aspartic acid, or arginine; monosaccharides, disaccharides, and othercarbohydrates including cellulose or its derivatives, glucose, manose,or dextrins; chelating agents such as EDTA; sugar alcohols such asmannitol or sorbitol; counterions such as sodium; and/or nonionicsurfactants such as polysorbates, poloxamers, or PEG.

[1198] The secreted polypeptide is typically formulated in such vehiclesat a concentration of about 0.1 mg/ml to 100 mg/ml, preferably 1-10mg/ml, at a pH of about 3 to 8. It will be understood that the use ofcertain of the foregoing excipients, carriers, or stabilizers willresult in the formation of polypeptide salts.

[1199] Any polypeptide to be used for therapeutic administration can besterile. Sterility is readily accomplished by filtration through sterilefiltration membranes (e.g., 0.2 micron membranes). Therapeuticpolypeptide compositions generally are placed into a container having asterile access port, for example, an intravenous solution bag or vialhaving a stopper pierceable by a hypodermic injection needle.

[1200] Polypeptides ordinarily will be stored in unit or multi-dosecontainers, for example, sealed ampoules or vials, as an aqueoussolution or as a lyophilized formulation for reconstitution. As anexample of a lyophilized formulation, 10-ml vials are filled with 5 mlof sterile-filtered 1% (w/v) aqueous polypeptide solution, and theresulting mixture is lyophilized. The infusion solution is prepared byreconstituting the lyophilized polypeptide using bacteriostaticWater-for-Injection.

[1201] The invention also provides a pharmaceutical pack or kitcomprising one or more containers filled with one or more of theingredients of the pharmaceutical compositions of the invention.Associated with such container(s) can be a notice in the form prescribedby a governmental agency regulating the manufacture, use or sale ofpharmaceuticals or biological products, which notice reflects approvalby the agency of manufacture, use or sale for human administration. Inaddition, the polypeptides of the present invention may be employed inconjunction with other therapeutic compounds.

Example 24 Method of Treating Decreased Levels of the Polypeptide

[1202] It will be appreciated that conditions caused by a decrease inthe standard or normal expression level of a secreted protein in anindividual can be treated by administering the polypeptide of thepresent invention, preferably in the secreted form. Thus, the inventionalso provides a method of treatment of an individual in need of anincreased level of the polypeptide comprising administering to such anindividual a pharmaceutical composition comprising an amount of thepolypeptide to increase the activity level of the polypeptide in such anindividual.

[1203] For example, a patient with decreased levels of a polypeptidereceives a daily dose 0.1 -100 ug/kg of the polypeptide for sixconsecutive days. Preferably, the polypeptide is in the secreted form.The exact details of the dosing scheme, based on administration andformulation, are provided in Example 23.

Example 25 Method of Treating Increased Levels of the Polypeptide

[1204] Antisense technology is used to inhibit production of apolypeptide of the present invention. This technology is one example ofa method of decreasing levels of a polypeptide, preferably a secretedform, due to a variety of etiologies, such as cancer.

[1205] For example, a patient diagnosed with abnormally increased levelsof a polypeptide is administered intravenously antisense polynucleotidesat 0.5, 1.0, 1.5, 2.0 and 3.0 mg/kg day for 21 days. This treatment isrepeated after a 7-day rest period if the treatment was well tolerated.The formulation of the antisense polynucleotide is provided in Example23.

Example 26 Method of Treatment Using Gene Therapy

[1206] One method of gene therapy transplants fibroblasts, which arecapable of expressing a polypeptide, onto a patient. Generally,fibroblasts are obtained from a subject by skin biopsy. The resultingtissue is placed in tissue-culture medium and separated into smallpieces. Small chunks of the tissue are placed on a wet surface of atissue culture flask, approximately ten pieces are placed in each flask.The flask is turned upside down, closed tight and left at roomtemperature over night. After 24 hours at room temperature, the flask isinverted and the chunks of tissue remain fixed to the bottom of theflask and fresh media (e.g., Ham's F12 media, with 10% FBS, penicillinand streptomycin) is added. The flasks are then incubated at 37° C. forapproximately one week.

[1207] At this time, fresh media is added and subsequently changed everyseveral days. After an additional two weeks in culture, a monolayer offibroblasts emerge. The monolayer is trypsinized and scaled into largerflasks.

[1208] pMV-7 (Kirschmeier, P. T. et al., DNA, 7:219-25 (1988)), flankedby the long terminal repeats of the Moloney murine sarcoma virus, isdigested with EcoRI and HindIII and subsequently treated with calfintestinal phosphatase., The linear vector is fractionated on agarosegel and purified, using glass beads.

[1209] The cDNA encoding a polypeptide of the present invention can beamplified using PCR primers which correspond to the 5′ and 3′ endsequences respectively as set forth in Example 1. Preferably, the 5′primer contains an EcoRI site and the 3′ primer includes a HindIII site.Equal quantities of the Moloney murine sarcoma virus linear backbone andthe amplified EcoRI and HindIII fragment are added together, in thepresence of T4 DNA ligase. The resulting mixture is maintained underconditions appropriate for ligation of the two fragments. The ligationmixture is then used to transform bacteria HB101, which are then platedonto agar containing kanamycin for the purpose of confirming that thevector has the gene of interest properly inserted.

[1210] The amphotropic pA317 or GP+am12 packaging cells are grown intissue culture to confluent density in Dulbecco's Modified Eagles Medium(DMEM) with 10% calf serum (CS), penicillin and streptomycin. The MSVvector containing the gene is then added to the media and the packagingcells transduced with the vector. The packaging cells now produceinfectious viral particles containing the gene (the packaging cells arenow referred to as producer cells).

[1211] Fresh media is added to the transduced producer cells, andsubsequently, the media is harvested from a 10 cm plate of confluentproducer cells. The spent media, containing the infectious viralparticles, is filtered through a millipore filter to remove detachedproducer cells and this media is then used to infect fibroblast cells.Media is removed from a sub-confluent plate of fibroblasts and quicklyreplaced with the media from the producer cells. This media is removedand replaced with fresh media. If the titer of virus is high, thenvirtually all fibroblasts will be infected and no selection is required.If the titer is very low, then it is necessary to use a retroviralvector that has a selectable marker, such as neo or his. Once thefibroblasts have been efficiently infected, the fibroblasts are analyzedto determine whether protein is produced.

[1212] The engineered fibroblasts are then transplanted onto the host,either alone or after having been grown to confluence on cytodex 3microcarrier beads.

[1213] It will be clear that the invention may be practiced otherwisethan as particularly described in the foregoing description andexamples. Numerous modifications and variations of the present inventionare possible in light of the above teachings and, therefore, are withinthe scope of the appended claims.

[1214] The entire disclosure of each document cited (including patents,patent applications, journal articles, abstracts, laboratory manuals,books, or other disclosures) in the Background of the Invention,Detailed Description, and Examples is hereby incorporated herein byreference. Further, the hard copy of the sequence listing submittedherewith and the corresponding computer readable form are bothincorporated herein by reference in their entireties.

1 672 1 733 DNA Homo sapiens 1 gggatccgga gcccaaatct tctgacaaaactcacacatg cccaccgtgc ccagcacctg 60 aattcgaggg tgcaccgtca gtcttcctcttccccccaaa acccaaggac accctcatga 120 tctcccggac tcctgaggtc acatgcgtggtggtggacgt aagccacgaa gaccctgagg 180 tcaagttcaa ctggtacgtg gacggcgtggaggtgcataa tgccaagaca aagccgcggg 240 aggagcagta caacagcacg taccgtgtggtcagcgtcct caccgtcctg caccaggact 300 ggctgaatgg caaggagtac aagtgcaaggtctccaacaa agccctccca acccccatcg 360 agaaaaccat ctccaaagcc aaagggcagccccgagaacc acaggtgtac accctgcccc 420 catcccggga tgagctgacc aagaaccaggtcagcctgac ctgcctggtc aaaggcttct 480 atccaagcga catcgccgtg gagtgggagagcaatgggca gccggagaac aactacaaga 540 ccacgcctcc cgtgctggac tccgacggctccttcttcct ctacagcaag ctcaccgtgg 600 acaagagcag gtggcagcag gggaacgtcttctcatgctc cgtgatgcat gaggctctgc 660 acaaccacta cacgcagaag agcctctccctgtctccggg taaatgagtg cgacggccgc 720 gactctagag gat 733 2 5 PRT Homosapiens Site (3) Xaa equals any of the twenty naturally ocurring L-aminoacids 2 Trp Ser Xaa Trp Ser 1 5 3 86 DNA Homo sapiens 3 gcgcctcgagatttccccga aatctagatt tccccgaaat gatttccccg aaatgatttc 60 cccgaaatatctgccatctc aattag 86 4 27 DNA Homo sapiens 4 gcggcaagct ttttgcaaagcctaggc 27 5 271 DNA Homo sapiens 5 ctcgagattt ccccgaaatc tagatttccccgaaatgatt tccccgaaat gatttccccg 60 aaatatctgc catctcaatt agtcagcaaccatagtcccg cccctaactc cgcccatccc 120 gcccctaact ccgcccagtt ccgcccattctccgccccat ggctgactaa ttttttttat 180 ttatgcagag gccgaggccg cctcggcctctgagctattc cagaagtagt gaggaggctt 240 ttttggaggc ctaggctttt gcaaaaagct t271 6 32 DNA Homo sapiens 6 gcgctcgagg gatgacagcg atagaacccc gg 32 7 31DNA Homo sapiens 7 gcgaagcttc gcgactcccc ggatccgcct c 31 8 12 DNA Homosapiens 8 ggggactttc cc 12 9 73 DNA Homo sapiens 9 gcggcctcga ggggactttcccggggactt tccggggact ttccgggact ttccatcctg 60 ccatctcaat tag 73 10 256DNA Homo sapiens 10 ctcgagggga ctttcccggg gactttccgg ggactttccgggactttcca tctgccatct 60 caattagtca gcaaccatag tcccgcccct aactccgcccatcccgcccc taactccgcc 120 cagttccgcc cattctccgc cccatggctg actaattttttttatttatg cagaggccga 180 ggccgcctcg gcctctgagc tattccagaa gtagtgaggaggcttttttg gaggcctagg 240 cttttgcaaa aagctt 256 11 1882 DNA Homo sapiensSITE (12) n equals a,t,g, or c 11 ttcggcacgg anactggaag gaaagaaagaaaggtcagct ttggcccaga tgtggttacc 60 ccttggtctc ctgtctttat gtctttctcctcttcctatt ctgtcatctc cctcacttaa 120 gtctcaggcc tgtcagcagc tcctgtggacattgccatcc cctctggtag ccttcagagc 180 aaacaggaca acctatgtta tggatgtttccaccaaccag ggtagtggca tggagcaccg 240 taaccatctg tgcttctgtg atctctatgacagagccact tctccacctc tgaaatgttc 300 cctgctctga aatctggcat gagatggcacaggtgaccac gcagaagcca ccagaatytt 360 gcctgcccta ttcctcctcc caagtctgttctcttattgt caacctcagc acaacaggct 420 ggcgccaatg gcattacaga gaaagcaatctgtgtggcta gtgggcagat taccatgcaa 480 gccccaggag aaatggagga gctttgtagccacctccctg tcasccagta ttaacatgtc 540 cccttccccc tgccccgccg taganttcaggacattcgcc cctgtgtgcc accaaaccag 600 ggactttccc cttsssttgg gttggcatccctgggctctc tcctggtacc cagcaagacg 660 tctgttccag ggcagggcac gagctttcaagctccgttac tatggcgatg gccatgatgt 720 tacaatccca cttgcctgaa taatcaagtgggaasgggaa gcasagggaa atggggccat 780 gtgaatgcag ctgctctgtt ctccctaccctgaggaaaaa ccaaagggaa gcaacaggaa 840 cttctgcaac tggtttttat cggaaagatcatcctgcctg cagatgctgt tgaaggggca 900 caagaaattg gagctggaga agattgatgaaagtgcaggt gtgtaaggaa atagaacagt 960 ctgctgggag tcagacctgg aattctgattccaaactctt tattactttg ggaagtcact 1020 cagcctcccc gtagccatct ccagggtgacggaacccagt gtattacctg ctggaaccaa 1080 ggaaactaac aatgtaggtt actagtgaataccccaatgg tttctccaat tatgcccatg 1140 ccaccaaaac aataaaacaa aattctctaacactgcaaag agtgagccat gcctgttaac 1200 actgtaaaga atgtaacatg tgggggacacacaggggcag atgggatggt ttagtttagg 1260 attttattag tgcatgccct accctctgggcgaacgtccc ctctgaggtt ttcttctcgg 1320 tggggggatt taacttctgt cctagggaaaacagtgtctg atgaggagtg tttccaacac 1380 aggctacatg aattccccta taccagtgcgaaagcagcca ggagtccccg ttggaaaaga 1440 acaatgccac tctcttttat gtatcttggttctgcaactc atttgttgta agtagggtta 1500 atcgagtatc aggttcacag tatcctgcccttattatttt atgattcact gactcaagtt 1560 ccacgaagtc cttagaaatg gacctcttcatgtaaaatat cttgagaata ataaatgtga 1620 gggaataaga aaggcaagct ttggacacagatatgatagg tgcatcagct tcggaagaga 1680 agaatgatgt gcagagtgtt aggaagacatccgggctgct gagactcggg attagaagaa 1740 agagaggtaa ataaagtggg tcctggaatcttttaggact tctgctgtag gacaaacagc 1800 tgcctttggt gttttaatgt ctcccaaagtacccttcagc caataaatac catctgttgg 1860 tgcaaaaaaa aaaaaaaaaa aa 1882 121590 DNA Homo sapiens SITE (1374) n equals a,t,g, or c 12 gggtcgacccacgcgtccgg agattctggg aggatcccga gtacccccca gttgcagtca 60 tgtcaagactgatgctcagg aggatcccaa ctgtcatgag caacacccat cgaacacagc 120 catccacctgggaacagatc aagaagctgt cacagatggt gggagaaaac ctgaggaaag 180 cgggacaaccagtcacaatg agtaatttaa tggtagctat gatagcagtg atcaccattg 240 ccgtgagtattccttcaaca agggctgaca cagagatcag ttatacttat tgggcatatt 300 tgtcaattttggctggcaat aatgcctgga tataatcact ttatgacaca gttacacatg 360 ctttctggtctcaatattta ccataataag tctgctccta taattgaggc ataccaccct 420 caaaaatctatttgtaaaca aaattgaacc tggccagaaa aaatgaatgt acttttttag 480 gaaggttgcattgcagaaca ggcagaggtg ctgcacaacg attcctatgg aatcattatt 540 gattggtcccctaaggggat gtttagcttg aattgcacct cttagtctgc atgtcacagc 600 cacactgtgttcaactggtc tgaacagaat ggtcagatgg tacaaatggt aagacgtatg 660 gcaagagttcctattatctg gaaccatggc agtatagggg cacctcaacc tcaaatgata 720 tggcccattgtaggagctaa acataaggat ttgtggcaac tgttaatagc tcttaataag 780 atcaaaatttgggaaagaat aaaaaagcat ctagaaggac actctgcaaa cttgtctttg 840 gatattgcaaaatatatata tatatttaaa gcatcccagg cacacctgac cttaatgcca 900 gaactggagtgctcgaagga gctgcagaca gattagcagc tagtaaccca ttaaaatgga 960 taaaaacacttagaagctct gtgatttcaa tgatgattgt gcttttaatc tgtgttgttt 1020 gtctttatatagtctgcaga tgctgatctt gactcctgtg agaagtagct caccgtgaca 1080 aagctgccttggctttttat cgctttgcaa aacaagagaa tggggacaag ttgggaacag 1140 gccccaaaatctggccataa actggcccct aaactggtca taaacaaaat ctctgcagca 1200 ctgtcacatgcttgtgatag cctgacgccc acgttggaag gctgtcggtt taccggaatg 1260 agggcaaggaacaactggcc cactcagggc ggataaccac ttaaggcatt cttaaaccac 1320 aaacaatagcatgagctatc tgtgccttaa ggacatgttc atgctgcaga taantagcca 1380 gagcccatccctttacntcg gcccatccct ttatttccca taaggaatac ttatagttaa 1440 tctatagaaacaatgcttat cactggcttg ctgtcaataa atatgtgggt aaatctctgt 1500 tcaaggctctcagctntgaa ggctgtgaga cccctgattt cccactccac aatctaaaaa 1560 aaaaataaaaacaaaaaaaa aaaaaaaaaa 1590 13 1373 DNA Homo sapiens 13 tcgacccacgcgtccgttca gaaaaaggat ttgacaaaat tcagtgccca ttcatggtta 60 aaaaaaaaaaaaactttcag aaaaatgata atggaggaga tctttctcaa cttgataaag 120 aacatctacaaaagccccta cagccaatgt aacacataat agtaaaagac taattgcttt 180 tctccaatatcagggatatt agggacagag atgtctgtcc tcaccactct tattcaacat 240 attgctggaagttctgtcta gtgcagtgag gaaagaaaag gaattaaaaa gcatgcagac 300 aaaaagaaggaaacaaaact gtctctattt gcaaatgaca tgattctcta aataaaaaat 360 cccaaggaatctacaaaaaa aactagagct aggtggggtg tggtggctca tgcctgtaat 420 cccagcactttgggaggctg aattaagagg attacctaaa ccaagaagtt caagaccagc 480 ctgcgcaacatagtaagacc cccatctcta caaaaaattg aaaaattagc tggatgtatt 540 agctactcagggagctgagc tgggagggat tgtttgagcc agagaggtca gggctctggt 600 gatccatgatcacatcacca tactccagcc tgggcaaccg agtgagacct gtccttaaaa 660 aacaaacaaaaacaaactag atctagtgag agttcagcaa gccctcaagc tacaagacct 720 atataccaaaaatcaacttg catttctata tactattaat gaacatatgg gaaacctaaa 780 tttaaaagatagtaccactt aacaattgtt tcacaaaaat gaattacctg ggcataaatt 840 aaataaacatatacaggatc tgtatgctaa aaattgcaaa atactgataa aagaaatcaa 900 agcaaacccaaagaagtgga gacacatacc gtgttcatgt actggaaggc tcagcagaga 960 cgtgggttccctccagactg atgtacaggt ttgatgtact tgctagcaaa aatcccagca 1020 aggtatttttttgtagatgc gcaagattat tctaaaattt gtatggaagg gcagtgaaac 1080 taaaagtcacgaaaataatc ttgaaaaaga aaaagaaaat gggcagaatc actgtatttg 1140 ataacataccttgttatata actgcagtaa tcaagacagt atagtgttgg tgaagggaca 1200 gacacaaggtcaatgaaaca gaatagagaa cccagacata gacccacaca agtaccacca 1260 gtggatttggacaaggtgca aaagcaactc attggaggaa ggcagcctat ttagccaatg 1320 tgactggagcactggatacc cataagccaa aaaaagaaaa aaaaaaaaaa agg 1373 14 1142 DNA Homosapiens SITE (341) n equals a,t,g, or c 14 tcgacccacg cgtccgtcttcctcctgcgt cctcccccgc tgcctccgct gctcccgacg 60 cggagcccgg agcccgcgccgagcccctgg cctcgcggtg ccatgctgcc ccggcggcgg 120 cgctgaagga tggcgacgccgctgcctccg ccctccccgc ggcacctgcg gctgctgcgg 180 ctgctgctct ccggcctcgtcctcggcgcc gccctgcgtg gagccgccgc cggccacccg 240 gaatgttgcc gcctgtcccgggagcctgga ctgtgccctg aagaagcggg caagtgtcct 300 cctggtgcac atgcctgtgggcctgccttc agcccttcca naaggaacag caaaggcttg 360 ttttgccang atgcgccgggcttcangcgg gggccgggcc caacccanac tngaaatgag 420 attgattcct ggcccaagggagcttgcccg gaaaggaatt tggacatcaa ttccgcccta 480 acccaaggac ggacagcggttcccggagct tgccaccttg ggattntcgg cacgggggca 540 ggggctggag ctgggcttcccttccactcc aggaaccccc acgcccacgc cccacacnta 600 ccatgggtta cccctgtgtcatccgacccg gtgcacatgt cgcccctgga gccccgggga 660 gggcaaggcg acggcntcgcccttgtgctg atcctggcgt tctgtgtggc cggtgcagcc 720 gccctctccg tagcctccntctgctggtgc aggctgcagc gtgagatccg cctgactcag 780 aaggccgagt acgccactgcgaaggccctg gctacacctg cagctacccc ggatctcgct 840 tggggaccag cgcctggcacagagcgcgga gatgtaccac taccagcacc aacggcaaca 900 gatgttgtcc ctggagcggcataaagagcc acccaaggag ctggacacgg ctcttcggat 960 gaggagaatg aggacggagacttcacggtg tacgagtgcc cgggcatggc cccgaccggg 1020 gaaatggagg tgcgcaaccatctgttcgac cacgccgcac tgtccgcgcc cctgccggcc 1080 cccagctcac cgcttgcactgccatgacct ggaggcagac agacgcccac ttgctccccg 1140 ac 1142 15 1034 DNAHomo sapiens 15 gaattcggca cgaggaacca ccttctgtag gacagtcacc aggccagatccagaaggctt 60 gaggccctgt ggtccccatc cttgggagaa gtcagctcca gcaccatgaagggcatcctc 120 gttgctggta tcactgcagt gcttgttgca gctgtagaat ctctgagctgcgtgcagtgt 180 aattcatggg aaaaatcctg tgtcaacagc attgcctctg aatgtccctcacatgccaac 240 accagctgta tcagctcctc agccagctcc tctctagaga caccagtcagattataccag 300 aatatgttct gctcagcgga gaactgcagt gaggagacac acattacagccttcactgtc 360 cacgtgtctg ctgaagaaca ctttcatttt gtaagccagt gctgccaaggaaaggaatgc 420 agcaacacca gcgatgccct ggaccctccc ctgaagaacg tgtccagcaacgcagagtgc 480 cctgcttgtt atgaatctaa tggaacttcc tgtcrtggga agccctggaaatgctatgaa 540 gaagaacagt gtgtcyttct agttgcagaa cttaagaatg acattgagtctaagagtctc 600 gtgctgaaag gctgttccaa cgtcagtaac gccacctgtc agttcctgtctggtgaaaac 660 aagactcttg gaggagtcat ctttcgaaag tttgagtgtg caaatgtaaacagcttaacc 720 cccacgtctg caccaaccac ttcccacaac gtgggctcca aagcttccctctacctcttg 780 gcccttgcca gcctccttct tcggggactg ctgccctgag gtcctggggctgcactttgc 840 ccagcacccc atttctgctt ctctgaggtc cagagcatcc cctgcggtgctgacaccctc 900 tttccctgct ctgccccgtt taactgccca gtaagtggga gtcacaggtctccaggcaat 960 gccgacagct gccttgttct tcattattaa agcactggtt cattcactgaaaaaaaaaaa 1020 aaaaaaaaac tcga 1034 16 1198 DNA Homo sapiens 16cccacgcgtc cgggagaaag ctgcactctg ttgagctcca gggcgcagtg gagggaggga 60gtgaaggagc tctctgtacc caaggaaagt gcagctgaga ctcagacaag attacaatga 120accaactcag cttcctgctg tttctcatag cgaccaccag aggatggagt acagatgagg 180ctaatactta cttcaaggaa tggacctgtt cttcgtctcc atctctgccc agaagctgca 240aggaaatcaa agacgaatgt cytagtgcat ttgatggcct gtattttctc cgcactgaga 300atggtgttat ctaccagacc ttctgtgaca tgacctctgg gggtggcggc tggaccctgg 360tggccagcgt gcatgagaat gacatgcgtg ggaagtgcac ggtgggcgat cgctggtcca 420gtcagcaggg cagcaaagca gactacccag agggggacgg caactgggcc aactacaaca 480cctttggatc tgcagaggcg gccacgagcg atgactacaa gaaccctggc tactacgaca 540tccaggccaa ggacctgggc atctggcacg tgcccaataa gtcccccatg cagcactgga 600gaaacagctc cctgmtgagg taccgcacgg acactggctt cctccagaca ctgggacata 660atctgtttgg catctaccag aaatatccag tgaaatatgg agaaggraag tgttggactg 720acaacggccc ggtgatccct gtggtctatg attttggcga cgcccagaaa acagcatctt 780attactcacc ctatggccag cgggaattca ctgcgggatt tgttcagttc agggtattta 840ataacgagag agcagccaac gccttgtgtg ctggaatgag ggtcaccgga tgtaacactg 900agcaccactg cattggtgga ggaggatact ttccagaggc cagtccccag cagtgtggag 960atttttctgg ttttgattgg agtggatatg gaactcatgt tggttacagc agcagccgtg 1020agataactga ggcagctgtg cttctattct atcgttgaga gttttgtggg agggaaccca 1080gacctctcct cccaaccatg agatcccaag gatggagaac aacttaccca gtagctagaa 1140tgttaatggc agaagagaaa acaataaatc atattgactc aaaaaaaaaa aaaaaaaa 1198 171447 DNA Homo sapiens SITE (1420) n equals a,t,g, or c 17 caagcgcgcaagggcgcggg cgagcaggcc tgtgaattcg caggatcatt tcagacccgc 60 acttcggcagccaactcgaa agcaggcggt tgtgtgcggc agcagttggc gtttgctttg 120 cacttcggaacctgttgcgt tttgacccac ggaggtggag gagtaacttt ttgacatgtt 180 ggcctttccagttttgttgg aagtttcatg gtcggttttg tttygtttct cattcttctc 240 tccksgcccctcagcccccc aacccccaac cccctcccgg tccgtgttgc atgcacgctg 300 ttcaaatgtgaggtctgaaa tggctggcac acgggaaaag ctgcttgtgt cattcgtttc 360 tgggagtgggatggctctga gcagcctcgc ctccctgttt gtactatttg aactttgcag 420 atctctgttctctcaagcag aactcccaac cagatccatt cttgaccagt gaccggctcg 480 gaatctggccttttgtgtga gatgatcacg gtttcttttg tttatcacgc catttgcaaa 540 tcagagcaagagctctttct caagggcaag aaacgcaaac aagaaatatt tgtgagatga 600 aagttgtcaattggattttc ttcctaaaca aacaacaaca acaaactact agaagtctcc 660 ctgagtccactcgcttggat ttctgacaca gtttacaaaa aaggaaaaag gcactgctcc 720 tattttcccttatggctgag ttcaccttaa gattgtaaat gtgtatatgt cagtgaaaac 780 attgaggcttggaaaatgtg ttattttcgt tgccctaagt ttgagtcgac tttagactca 840 aaaacattttgagcgaatat caaagttaac ttttaaaaat tgcgaaacta tttcagaatc 900 gcaattttatcgaagattaa atcagacttt tttgtctggt aattatatat ttattattta 960 gcaaaactgaagaaaaaaag cacagaattg tttcaacaga tgtctctcat tttcagctag 1020 catttctctcccaagttgag ctggtttaat gtgttttgga tttccctcct caattggctt 1080 attttttagatcacctgcaa ttcatttgca aattgcaata aaacacattt tagaaaaaag 1140 gaaccttcaattattagctt tgtttctttt taaatgtata taaaaagact aatgtttgtg 1200 aatgaagttggctaacatgt atttagtttc attttggctt tatgtaatat aaagttttta 1260 aaattttaaatatggtttta acctttatgt gtaaatgatt ttctagtgtg accttctaat 1320 ttaatattagacgtctaagg tatatctgta aattagaatc cgactatcac tctgttcatt 1380 ttttttgaacaaagagttta aataaagcct gaaccagggn acagataaag anaatnaaaa 1440 aaaaaaa 144718 1422 DNA Homo sapiens SITE (1397) n equals a,t,g, or c 18 gtttctcttaggttttgaag gtataagtgt aaagtgaagc atctctcgat gattctttcc 60 aagataggtttaaaaactat gaatccattt tcagtattty cttctctctg tttgaaacag 120 tttgaggatgtgtytctttt tcttggcttg atgtttggta sgtccttgaa tgggcaagag 180 ggcacatgaagtacggcgtc ctccacattc acggcctcta cacgggaccc ctgcggggtg 240 ggtgctggacccatcggggt ataaagacgt cactcaagac gcagaagtca tggaagtcct 300 ccagaacttataccgcacca agtcctttct gtttgtgggc tgtggggaga cccttcgtga 360 tcagatattccaggccctct ttctttactc cgtgccgaat aaggtggatt tggagcacta 420 catgcttgtgctgaaggaga atgaagacca tttctttaag catcaggcag atatgcttct 480 gcacggaatcaaagttgtat cctacgggga ctgttttgac cactttccag gatatgtgca 540 agaccttgccactcagatct gcaaacagca aagcccagga catttgtact cgaattcatg 600 gagtgccactcctgatggga gaggaggccc atgacagtga cagtcatgct agtgatcgcg 660 gacaccacaccatgctgcct ttgccagctg gctccttcag cgagtcctcg caccaagcct 720 gggaggtagagatgctgatc gcgtggacag caccacatta ttgggtaatg catgccagga 780 ctgtgcaaagaggaagttag aagagaatgg aattgaagtt tcaaaaaaac gcacacaatc 840 agatactggtgtctgtgcca tcctcatgct cgcgggagtt ttggcatggg attctccgtt 900 gtgattcccccggactccac tgtctgaaga ccaggtttcc tatgaagagg gtctgatggg 960 aacctgttcccagtgatttg aagatgatgc tggagggtct tgaaatcttt acagtaaaac 1020 ctgcaacttgaaaactagcc tttctgtaac cacagtgccc aaacgaagag gaatgtatgg 1080 agaactccacgtggatctct gattgggaaa ccgtcacata caccaagaga gccacatggg 1140 catgtggccctcaaggctgg gtgagagggc tcccctgtgt gttgaactat gcaggagggt 1200 gacgcggacacatttcaggt ggactttgca aggactgatg gatagctacc tcagggacca 1260 gaatccgtgggaagggatgg acctggtgtt cccgttccca tctgacaggc tctcttttgt 1320 ccaaggtggtatttttcgta ataaaagggg aagagtaaar amwrwmmaar maamagtagc 1380 tgccaaagagaaaatangaa atagacactt tttttttttg gg 1422 19 1107 DNA Homo sapiens 19ctaaactatt tagttcaaaa gtaacccaac taattaaagt gaaaaaaaat tgttgaatca 60caatgaacaa acataaaaca atacttaaat gagaattctg tgtctttttt ggttttatct 120gtgatttatt ttgtccagta ttaaggaatg gttatcttta tcattcttct aacatgtttt 180ggtttctcta atggttcatt ttcctttagc ttgtgaaaat tagggcagtt tgtccagagc 240cttactcgca ggagacacca gacccaaccc atgcttagat ttctgttaat aaaagggaga 300agggtatttg aataggtagt aaaggcaggt acaagtttaa gggagcaggg ctatcatatg 360tactaggtga gattactata aatgtctgaa aagttacatg catagtcatt ggctcaggta 420atttctctga atttgaactt atttgattta tttaaccaag ttattataat atgcagttct 480ctttaatcaa tcttctatta ttcaatcatc tatccattta ttaattcaac aaatatttat 540taaagtgcct accatgatta tgtgctgtag aaaagacaag gacatttact aggggggatt 600gtgggcccaa tcggcatcat aagcatgttc tgaaagccaa agacaataat cacatccaac 660ggcaccagtt cagctcaact ttagaattca gcagtaacag tacagatggc ctaaagtaca 720tctgtgtgta tctgtacgtg tgcacacacc catgtatata tatttatcta tctgcacaca 780cactacatat gtatacacac tatctatgta aaatataata tatgtataat gcatataaat 840tctaacaagt gtatttgtgt tatctttaaa atagaacaat tgtatcttga agtggtaaat 900gcagagaatt ggttttattg ttgatctgtg gatttaatga tttctaggtg aaaaggacgt 960ttaagtgtac aatttctttt cttaatttaa tatatttatg taaatgcatg cctgaaattt 1020ggttagattg gctgtgtttt gtgtctttta acatgatcaa atgattaaac tttatgctta 1080tgacttgaaa aaaaaaaaaa aaaaaaa 1107 20 1183 DNA Homo sapiens SITE (266) nequals a,t,g, or c 20 gtgattcaaa gccatcacaa aacactataa gactgaccaaaatttagata acctttgaac 60 cacgattttt ttccacatct gtytgtgaga cacagcgcaatgctactgcc cttccagaaa 120 ctgtgctaaa aagagaaagt ccaaaagact ctaaacaaaaacctcgacgc cgttgaggat 180 gtgtttcatt ctggtggtct gttttgcaag cttgataacagaatgtccgt gccattgtaa 240 atgttgtaga gatgtgggcc gtggcncaac cgtcctatatgwgtgtagca tggtacagaa 300 caaactgctt acacaggtct cactagttag aaacctgtgggccatggagg tcagacatcc 360 atcttgtmcm tctataggca agaagtgttt ccagatcctttggaaaggtg ggcatggggc 420 aggtsnttgg agagtggcgt ttgagcagag cgaccccatttccgtgtgaa ccataggcac 480 aacccaggaa gtttccccac ttgtaggagt gtgggtattccagagcaaga ctgtggccac 540 catcttcccc tcttggtgtt ttccgaaagt gacagtgttggtcatcccat gaccactgaa 600 gcttagtaac cagcgccaaa aagtagattc atcaaactagagaccccagc tccccttctc 660 gccatcttct ttctcaagtt gaccgtggtg ctgtttctggaaggcatctg caactccaag 720 tccatgcaga actctggaag gccaagttca tcgcagcatgttcaccatat cccagcctcc 780 aaatctatcc tcctaccttc caacgcatga cctgttggggagcagagact taacccccaa 840 ctcagaggaa cccttcctcc agcgtctttg gcatggtttctagggtgaga gttcccaatt 900 tggatagaac ggccaccata ttggttactg aatctctctcccttgttttt attacgtttc 960 ctttttcaaa ctgtccatgg gaaggctgaa ttgagtgactccccagaatg aagatgagaa 1020 ggtgaatata atcaatgcca atgtaatgcc agcgggtgargatggccgat ggraggtttt 1080 caaagatgta gctagcattt tggaaaccat atgggcaaaacccgggcaac cagagggggg 1140 aacaggttaa gggaccgttt cccaggaaan tccccaanttttt 1183 21 1420 DNA Homo sapiens SITE (524) n equals a,t,g, or c 21gtctgcatcc cgggcgcggc tgggttgagt gttctcttag gaatggtgga gaactgggtc 60cttgaggagt caccggggag actgctcgca ctgtttgtgg tgcgacgggc actggcccag 120ggacagaggg aagagaaggg ccagccagcg gcagtggagt cggcaggctg gctgcccact 180cgctttctct cctcacaaga ctcgcttccc ctgtcttcga ggatctcgaa cggactatag 240tctggactcg ctgggctgga ggaaacttgg ccgctggcca cccggaggag actgaaaatc 300ctttggtcaa cagggcgcct ttccttgaac caaaacaaaa ctttccgaag ccggaaagga 360aacgcccagt gtcgcctgag agccctggag ctgcgcgaga cccaggcact gagtgcggcc 420tcggcctctg acctctaaca cgccgggaac aaaccatctg gggcggcccg caggcctgcg 480ggagcggaat gtgacccgaa accgaccgac ttcctgaccc atantccata gttctcttca 540gcaacttgaa cattttggaa aaagaaacaa tcttaacatg ccacnaccta atgganaaac 600taaatcccct tcctacacct tgctttccaa aagttaaaaa aaaatagtta aacgctatta 660gaggtctcaa gttcactgtc accagatcag ctaggtccag aatcttcagt tcttgaagcc 720aagccctaca aatagattta ttgtagcata tcacacctct tcaggtgact taaaacaatg 780agaattcatg agaaattatc ttcatcctca agtaaaaatc atgaggtgcc tttcacatgg 840atgaaattgt aagtgcttgt tgaacaagga ataattggat aatggtattg tggtcatact 900ttttaagaat atctgttaga aagatatagg atgcagaaca tctaggattt gctgaaagtc 960atttattatg gatagggggt atgagtaagt tcatagatga aaagggatga aacaagattg 1020gccatagttg ctctattttt gngtatcttg tttctttatt tngtttcttt aaaaagtcct 1080catatcactg acatttacac ttagttttag ggaaagtcaa atttagaaat aagctacagc 1140tctntaagct atcggtctaa ctggattttt ntcgatgctg aagaactttt taaaaaattc 1200agccatttag gtcacacagc aaatacattt ggcattaaat tcctagtatc actaaagtac 1260tccctcccac cgccgcgccc cccccnttcc ccccgcaccc ttagacctgg gcaagagaga 1320cttctatcct ggactccatg ctttaaaggn acttacatat cacacacaca cattaattta 1380aaaaggaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1420 22 1575 DNA Homosapiens 22 gtccattctt ccggtggaga tggctgcggc cgtggcgggg atgctgcgagggggtctcct 60 gccccaggcg ggccggctgc ctaccctcca gactgtccgc tatggctccaaggctgttac 120 ccgccaccgt cgtgtgatgc actttcagcg gcagaagctg atggctgtgactgaatatat 180 ccccccgaaa ccagccatcc acccatcatg cctgccatct cctcccagccccccacagga 240 ggagataggc ctcatcaggc ttctccgccg ggagatagca gcagttttccaggacaaccg 300 aatgatagcc gtctgccaga atgtggctct gagtgcagag gacaagcttcttatgcgaca 360 ccagctgcgg aaacacaaga tcctgatgaa grtcttcccc aaccaggtcctgaagccctt 420 cctggaggat tccaagtacc aaaatctgct gccccttttt gtggggcacaacatgctgct 480 ggtcagtgaa gagcccaagg tcaaggagat ggtacggatc ttaaggactgtgccattcct 540 gccgctgcta ggtggctgca ttgatgacac catcctcagc aggcagggctttatcaacta 600 ctccaagctc cccagcctgc ccctggtgca gggggagctt gtaggaggcctcacctgcct 660 cacagcccag acccactccc tgctccagca ccagcccctc cagctgaccaccctgttgga 720 ccagtacatc agagagcaac gcgagaagga ttctgtcatg tcggccaatgggaagccaga 780 tcctgacact gttccggact cgtagccagc ctgtttagcc agccctgcgcataaatacac 840 tctgcgttat tggctgtgct ctcctcaatg ggacatgtgg aagaacttggggtcggggag 900 tgtgtttgtc acttggtttt cactagtaat gatattgtca ggtatagggccacttggaga 960 tgcagaggat tccatttcag atgtcagtca ccggcttcgt ccttagttttcccaacttgg 1020 gacgtgatag gagcaaagtc tctccattct ccaggtccaa ggcagagatcctgaaaagat 1080 agggctattg tcccctgcct ccttggtcac tgcctcttgc tgcacgggctcctgagccca 1140 cccccttggg gcacaacctg ccactgccac agtagctcaa ccaagcagttgtgctgagaa 1200 tggcacctgg tgagagcctg ctgtgtgcca ggctttgtgc tgagtgctgtacatgtatta 1260 gttcctttac tgctgaccac attgtaccca tttcacagag aaggagcagagaaattaagt 1320 ggcttgctca aggtcatgca gttagtaagt ggcagaacag ggacttgaaccaagccctct 1380 gctctgaaga ccgcgtcctg aatttcttca ctagagcttc ctcatcaggttacccagaag 1440 tgggtcccat ccaccatcca ggtgtgcttg gatgttagtt ctccaccctcgaggtgtacg 1500 ctgtgaaaag tttgggagca ctgctttata ataaaatgaa atatattctamaaaaaaaaa 1560 aaaaaaaaaa ykcga 1575 23 541 DNA Homo sapiens 23caggagcaag gctttgtgct atatctacat aatcttagac cctgttcctt ccaattccag 60ggatatgctc ttaaccactg cagtataagc ctccccgcya cactctgagt ggagcagagg 120aaggtgtttt tgtctttgag aaaggcaagg atgaagggca agatttgagc catggtggta 180gatcagaaag aagatctgat aacaggctta gggatcaaaa tggtaaggaa atggcttcag 240gggagtcagg cctggcccct ggagagggag gagagggaag ggctaggctc tttatgtaca 300tgctgtccat ggggcctggt aagattcmtg gaatcactaa cccatttcac aggtgaggca 360attgagcctc tcagagctga agtaactgac ccaaagcatc cgtgctcttg tgtggcagag 420ccagaagtca aatccaggtc tctgtgamct caaggggcac caaartgagt atcaaaaagg 480cagaaaggga cttatccctt cactcactca gcaaaagcat agtaagcagg tggcgtgcct 540 t541 24 833 DNA Homo sapiens 24 gatcttgtcc aagcagtcgg ggctacttccaagaatgtca gctcctgtta gcaaccagtg 60 gagtctggcc ttgggctcta agttgacctctctatagctc caaatcctac caatctcaga 120 aaactgtaag aggcacagat gactccaccagctgcagagt gactctgaag agagtcttca 180 cttactgcac aggcaaagaa aggcacaggaatatttccta cctctccctc ctgtgagtcc 240 cacctccccc cacccccatc tccaggaggcaggtagagca gttctraccg agaggataga 300 ctgctgttgc tgtctttccc cagctctgaactagttttaa ggtagcttag gatgaaaaat 360 ggagaatgat tgggggttcc aaaccactttyttctccctt ggcttatatc tcttcaccat 420 ttggtggtca actgtgggsc taccctggacctcatctact cagcgagaat tggacatgaa 480 gctagaggca gctgccttgg aagggaagtmaggctcactt ggacagccca ggccatggca 540 ggaagaatcc cttcctcttg gggtccttgatgggcatgtg tgatggggaa ggagcagtct 600 cccagccctg ggtctgctcc ccacatctctcctaattcca cttcaccttt tgccaccccc 660 tccccaccag aggcctagcc cttttgtcaccgaaggcccc cagagtgttt ctgtgtgaaa 720 ccctctcatt tacactgtgg catcaaaatccacaaaagat ggattaattg cactctggtt 780 aatagcagca gcacaatgat taaaatctatattcctaaaa aaaaaaaaaa aaa 833 25 1555 DNA Homo sapiens SITE (1248) nequals a,t,g, or c 25 ggcacgagct gggcagatgc aaaatctgga gagcgcgagggccgggcggt cagtcagcac 60 ccagactggc agcatgaccg gtcagatacc aaggctttctaaagtcaacc ttttcactct 120 gctcagcctc tggatggagc tctttccagc agaagcccagcggcaaaaat ctcagaaaaa 180 tgaagaggga aagcatggac ccttaggaga taatgaagagaggaccagag tatctactga 240 caaaagacag gattactggg agcagctaag atgcctaratgaaaggttta ccatcactgc 300 tggttaggaa atggattatg agaactcgaa cagagggaaggtgaaatgca accggaggaa 360 acactctgat atgaggtttg aggccttcaa aattgctttgcagcataagc cacagtgagt 420 caggagtacc agggagtgga tagaatgttt atttgtttaactgagacttt ttagttcatc 480 aattattttg aagggtagaa cactctgtgg gctctctttctatttccttc tgggtacaat 540 cacaaaaaaa aaatctctcc tagctgaaat tacatgcagtactagcaaag ggtctctttg 600 ttataaactg ttcattaatt gacgaacatt tgtgtacttaactatgtata aggcatctca 660 tcgttcaatt tcaaatacaa attaaaatat tttttcacatttgttatcct gttatgtttt 720 ctcttttaca aattgtctgt tcgtatcttt ttgtctctctttaggcctta ttcttgtcaa 780 ttcatatgtg ctctaatgaa ttgaaatatt ttctgtatattaaacattac taacctttcc 840 tctgtcacac tgattgaaaa atgatctatt tagtttgttgttttgtcttt aattttgtaa 900 gctttaaaaa gttaatattg cccttcagac accatcccaacatcacataa gaattttttc 960 atgttataaa ttctttgtgg acatatttga taactgttttattatgagga ggaccataat 1020 taattcaacc attcccctat tttggtcatt taggtttttgggtttgggtt ttttgtttgt 1080 ttaacgtctt tgcttgctat tttaaagaat gctgcactaaatgtgaatgc ttgagatttc 1140 ttctctgtat ttagaatatt ttcctagaat ggattctcagaagaattctc agtctgtgga 1200 gaggaacatt tttaatgcat ggaagagctg gagtgaaccgaatttcanac tgccctgctg 1260 atccagaaat aagtttgctt acggaggctt ctagttctgaagatgcaaag ttagatgcca 1320 aagcagtgga aagattgaag tcaaacagtc gggcccatgtgtgtgtctta cttcaacctt 1380 tggtgtgtna nanggngcag tttgtagagg agacctcttacaaatgtgac tttattcaaa 1440 aaattacaaa aacattgccg gatgctaaca ctgacttttattatgaatgt aaacaagaaa 1500 gaataaaaga atatgaaatg ttaaaaaaaa aaaaaaaaaaaaaaaaaaaa naaaa 1555 26 1543 DNA Homo sapiens SITE (69) n equals a,t,g,or c 26 gagcgggata acaatttcac acagggaaca agctatgacc atggattacgccaagcttgg 60 aattaaccnt cactaaaggg aacaaaagct gggagctccc accgcggtggcggccgttct 120 agaactagtg gatcccccgg gctgcaggaa ttcggcacga gccgaacagtaggacatgtc 180 atggcatttt tgctcaccct tgttccactc ctccccagcc gttgtcttggtttggaggag 240 atggcagttc ctaattccac ctgtattagt ccattctcat gctgctatggataaatatct 300 aagactgggt aatttataaa ggaaagaggt ttagttgact cacagttctgcatagctgag 360 gagacctcag gaaccttata atcatggcaa aaggcaaagg agaagcagacaggacagagt 420 gaatgccagc aggagaaatg ccagacgctt ataaaaccat caaatcttgtgagaactctt 480 cactatcata agaacggcat ggggaaaact gcccccatga ttcagttacctccacctggt 540 cccacccttg acatgtggga attattacaa ttcaaggtga gatttgggtggggacacaca 600 gccaaatcat atcaccatcc cttgaaccaa aacgaacaag gctgaccttatttgcaacat 660 tctaacttgt ctaaaggctg cctgaagaat tgatccctga ttcacctaactcagatntct 720 gctaggagac aagcatggcc ttaatctcag atgaggagaa gcagtagtcatggctcagaa 780 agctgcagag agaccctaca gattcctggg gcaaaagatt ataggtggagacatatgaca 840 gaccatcaag accccacaaa gatctcttgg gaaatttaag acaattaaaagcagccatnt 900 atacagagat tcaaaaaacc acaaacaggt ccaggcaagg atgcatgctcagtaaagacc 960 tgagaagacc tttagctttc tctttgatgt gatctcaaaa ttcagaagcaaggccaagat 1020 aattaggaaa ggacttccat ggcaaagagc cagtctacag agaatgggagaagtagctgt 1080 ttttcttttt gttttcaaat ccccaacata actattgtga atttaaaatcccaaaatcac 1140 aatgcataaa aagaaacgga aacatggacc attcaataat aataataaattggcagaaac 1200 tatccctgaa aaaatacagg tatcagactt actagaaaaa gattttcaaacaatgtttta 1260 aatatgttca aacagtaaag aacaacatgg acagagacct aaaggaaatcaggtaaatta 1320 tatgaacaaa ggggaatttc aacagagata gacattatta aaagaaccaaccagaaattc 1380 tggaaatgaa aaatataatg ggcacactgg ggatagtcaa acttaaaaattcactagagg 1440 gattcaatag cagacttgga cagaagaaag aataaacaag cttaaagataacttatttga 1500 aattatctag tatgaggtac aaaaaaaaaa aaaaaaaaaa aaa 1543 271262 DNA Homo sapiens SITE (621) n equals a,t,g, or c 27 ggcaccagaaaaaaaaaaga taatccaaag aatttaaatt gtaatcatgt ttcatgtatt 60 tgttttattacttactttta tagcacttag tcccagtggt attagactgc tatttggttt 120 catacaaaaaggattaaatt taaattcatt catgtttaga cttgagttat tacattttta 180 aaactatcatcttgccttta atgtttgtgg tcctacacaa actattagta catttcagta 240 tcctcttacccctttgtttt taagtttttg attgctaaag caagactttt ttcttctaga 300 atttaagtcaaccaagtgtt atctatgttg taaaaatgga taatagtaga ttttaggtga 360 taaaacaacttgttagtaag acatttccta gcttaaaaaa aaaaatcaaa aattccatga 420 tagaaatgcagacctgtgag ggaaactcct gaaaagcata agaagcatcc cagagagcca 480 tgggttttctagaccagaga atttagaggg agattgtgga actgaggctt aggtggtcag 540 atcgtttcccttatcactgt aatattttct gggggaaaaa tgctttctga gttgtttaaa 600 caagcatccttacatttttt ntttaattaa aacagcctgt ntagggcttg ggattcccta 660 atactacagtagcagtatat gaatatgatt ttgtgattgt gttttttaaa agataagtaa 720 tnngangaantgttcttttg cagtcagaaa acactcacaa aaagacaaaa aaagttccac 780 agtattatatttcatgtcag ttcaggccta aaatcctttg caaataagat gtttataggc 840 tggtcacaattaacaatgtt attattggca gcacttcttg gatggatacc ttttgggacc 900 tttcattagaaagagggaaa gaatggggtg gttttgtatg ggctcctgtt tggggtaaaa 960 atagcagagtcagttgctga ggaccaatga cctttcctta taaacattta gtttcatacc 1020 catattaggtcttgtcttga ggacccttta tatgtgcttg tttactagtg gccttccagc 1080 catagcattcttaccttttt ttcctattct aagaattaaa aaaaaaaatt atagagccag 1140 caagggaggaggcaggaaac agaaatcgaa tttcatcatt ccagtatagt tgtccctttt 1200 tttgtatttctgacttggtt ttataattat atttacttac taaaaaaaaa aaaaagggna 1260 na 1262 28753 DNA Homo sapiens 28 ggcacgaggt gatgacttca ctcccaattc tggcatttggggctgtctat tggccagacc 60 ttgcttcaca tagtttctca ccctcaagga gtctagcccagactccccat atgtcagtct 120 cagggtagca tttcaagagg gataaggtag acgtttctggcctgttgtgg tgtaggctgt 180 gaattaccat aacatcactt ctttgagatt ttcttggtcaaggcaaatca catgacaagg 240 actcaagagg gtagagaaat aggttctact atttagtggaaaggacagca aagtgacatc 300 acaaagagga atgcatatag agatgggggg aatatgtgaccaactttagt aatcactgta 360 attctgaatt gactcacaaa cactatcaag acggatcattgtcataccct agttcaaaaa 420 gcagtccttg cagcaataca gaacagatag aagtgaagagaatgtgattt tgctaaaaat 480 gacatattta catgaccagt gatgggtgag acctatgaaaaatccccaga gattctcaag 540 aactcataaa gtgcatttcc atatttatgt agaatatcaatctcctgctg tctttgactt 600 cacctagtat attcctaggt atgtgtatct aagcccaagttggtctcacg tttttgccta 660 cttccgagtc aatatgtgac atgccatccc acctttttgtgttaccacat tattataaca 720 taaggggtgg ttatgtttcc tggatatctt gag 753 291621 DNA Homo sapiens SITE (527) n equals a,t,g, or c 29 ggcacaggcgcggcctgcgg cttcttggga actctagggc cgcggccggg cctggctctg 60 ccggcggcctgttgggagct ggatcggagc ggtttggaac gacaagcccg acaaagagac 120 ttttaaaaaaccatggcaga tgtggaccca gatacattgc tggaatggct acagatggga 180 casggragatsaaaaggaca tgcaactaat accccttgaa cagctatgca tgctgctttt 240 gatgtctgacaacgtggatc gttgttttga aacatgtcct cctcgcactt tcttaccagc 300 cctttgcaaaatttttcttg atgaaagtgc tccagacaat gtattagagg tgacagcccg 360 tgccataacatactacctgg atgtatctgc ggaatgtacc cgaaggattg ttggggtaga 420 tggagctataaaagcacttt gtaatcsttt ggttgtagtt gaacttaaca acaggactag 480 cagagacttagctgaacagt gtgtaaaggt attagaactg atatgtnctc ctgagtccgg 540 ancagtctttgangctggtg gtttgaatcg tgttgcttac cttccaagcg tgaacagtgg 600 acatctagttcataaagaca ccttgcactc tgctatggct gtggtatcaa gactctgtgg 660 caaaatggagcctcaagatt cttctttaga aatttgtgta naatctctgt ctagtttatg 720 aaagcatgaanatcatcagg tttcagatgg agctctgcga tgctttgcat cactggctga 780 ccgatttacccgtcgtggtg ttgacccagc tccattagcc aagcatggat taactgagga 840 gctgttatctcgaatggctg ctgctggtgg tactgtttca ggaccatcat cagcatgcaa 900 accagntcgcagcaccacag gagctccatc caccactgca gattccaaat tgagtaatca 960 ggtgtcaacaattgtaagtc tgctctcaac actttgcaga ggctctccgg tagtaacaca 1020 tgatcttctgaggtcggagc ttccagattc aattgaaagt gcattgcagg gtgatgaaag 1080 atgtgtgcttgatactatgc gtttggttga ctttctcttg gtgctattat ttgaaggacg 1140 aaaagctttgccaaagtcta gtgctggatc tacaggcaga atcccaggac tccggagatt 1200 agatagttctggggagcgct cacatcggca gcttatagat tgtattcgaa gtaaagatac 1260 cgatgcacttatagatgcaa ttgacacagg agcctttgaa gtaaatttta tggatgatgt 1320 aggtcagactctattaaact gggcctctgc ttttggaact caggaaatgg tagaatttct 1380 ttgtgagagaggtgcagatg ttaatagagg tcaaaggtca tcatcattac attatgctgc 1440 atgttttggaagacctcaag tagcaaagac tctgttacgg catggtgcaa atccagatct 1500 gagagatgaagatgggaaaa ctccattaga taaagctcga gaaaggggcc atagtgaagt 1560 ggtagctattcttcagtctc caggtgattg gatgtgtcca gttaataaag gagatgataa 1620 g 1621 30921 DNA Homo sapiens 30 ccacgcgtcc gaccatgcca aatttcttgt ggttccctaaatgcgccatg tttgaagata 60 ctctgaggac attgtatata cttttgttct acctgagatacatttgctta ctttctccac 120 atattgccct catgacactt atccttattg atggatttcttcaatgctac tattgtgcct 180 tacatgtgcc ttgtattata gcatttttat agcatttctcacccaattgt ggctatttgt 240 ttacatgtct gtctccttgg tggaactgtg aactctgtcataacagatgc cattttatgt 300 cagttagact tctttggttg ccagtaagag aagctgactctaatctaaac caaaaggaat 360 tcattggacg gatgtgggtt ggctcacaaa atcaaagggacaactgcgga ccgatcttgg 420 aatgatgctc tgacaccaga acagctctgt gaattcagataggggtagtg aattgaccat 480 ttcatcaaat gctgcagcaa gctaggtggt ttccccaaaggaaattgagg agtgttacaa 540 gaagaccatt aggggaacgg ttatctggtg gctgataataacaaatttcc atggcagtct 600 ctttgctctc tgttggaaga ggtactccac catgggccttgagcatctct acacatcctt 660 gctaagcgtg tcaaatttca agtcctaact gtcctctgtctctggaggag gagacaggtt 720 tggttactgt ttgttgtaaa aattactgag cccttcaccatgggtgcctc agctgtatgc 780 aaagcccctt gtattgctgg gggacagagc aactggtactgccatgctgg tgctctggct 840 gtttgctgtt ggcaataaac tattctgttt tggttcaaaaaaaaaaaaaa aaaaaaaaaa 900 aaaaaaaaaa aaaaaaaaaa a 921 31 2095 DNA Homosapiens SITE (14) n equals a,t,g, or c 31 cccacgcggt ccgnatcgtccttccctcac ttcagagggt ggccagagct gaatacccag 60 agagggacaa gtaagggtccagttccaaaa catcatgagg atgtatcatc ccacgtgtct 120 cacctgacag ttacagaggaaacccgcacc cagaatgcac gtgctgtctt atgggaacac 180 tcagcgcaga gtgctcaggtccggccacac tcgggctgtg cttggtcgtg ccatggaatt 240 cctcaggact ttctcagcctccctaatggc agaagcccct ttacagcaag acatttaccg 300 tttgtctgaa aatagccgaactgagccttt tcttcaggct atatgagaag tctctagaca 360 gtgggcaccg tcagaaagcccagagccttg tgatagctcc caccctgcct ggctcagatc 420 ttcccatttt tttcctctggcactaacctc accttttgtt tttttgtgtt tgtgtttgtt 480 tttgtttttg cagagttggattacagaaac tcctatgaaa ttgaatatat ggagaaaatt 540 ggctcctcct tacctcaggacgacgatgcc ccgaagaagc aggccttgta ccttatgttt 600 gacacttctc aggagagccctgtcaagtca tctcccgtcc gcatgtcaga gtccccgacg 660 ccgtgttcag ggtcaagttttgaagagact gaagcccttg tgaacactgc tgcgaaaaac 720 cagcatcctg tcccacgaggactggcccct aaccaagagt cacacttgca ggtgccagag 780 aaatcctccc agaaggagctggaggccatg ggcttgggca ccccttcaga agcgattgaa 840 attagagagg ctgctcacccaacagacgtc tccatctcca aaacagcctt gtactcccgc 900 atcrggaccr ctgaggtggagaaacctgca ggccttctgt tccagcagcc cgacctggac 960 tctgccctcc agatcgccagagcagagatc ataaccaagg agagagaggt ctcagaatgg 1020 aaagataaat atgaagaaagcaggcgggaa gtgatggaaa tgaggaaaat agtggccgag 1080 tatgagaaga ccatcgctcagatgatagag gacgaacaga gagagaagtc agtctcccac 1140 cagacggtgc agcagctggttctggagaag gagcaagccc tggccgacct gaactccgtg 1200 gagaagtctc tggccgacctcttcagaaga tatgagaaga tgaaggaggt cctagaaggc 1260 ttccgcaaga atgaagaggtgttgaagaga tgtgcgcagg agtacctgtc ccgggtgaag 1320 aaggaggagc agaggtaccaggccctgaag gtgcacgcgg aggagaaact ggacagggcc 1380 aatgctgaga ttgctcaggttcgaggcaag gcccagcagg agcaagccgc ccaccaggcc 1440 agcctgcgga aggagcagctgcgagtggac gccctggaaa ggacgctgga gcagaagaat 1500 aaagaaatag aagaactcaccaagatttgt gacgaactga ttgccaaaat ggggaaaagc 1560 taactctgaa ccgaatgttttggacttaac tgttgcgtgc aatatgaccg tcggcacact 1620 gctgttcctc cagttccatggacaggttct gttttcactt tttygtatgc actactgtat 1680 ttcctttcta aataaaattgatttgattgt atgcagtact aaggagacta tcagaatttc 1740 ttgctattgg tttgcattttcctagtataa ttcatagcaa gttgacctca gagttcctgt 1800 atcagggaga ttgtctgattctctaataaa agacacattg ctgaccttgg ccttgccctt 1860 tgtacacaag ttcccagggtgagcagcttt tggatttaat atgaacatgt acagcgtgca 1920 tagggactct tgccttaaggagtgtaaact tgatctgcat ttgctgattt gtttttaaaa 1980 aaacaagaaa tgcatgtttcaaataaaatt ctctattgta aataaaattt tttctttgga 2040 tcttggcaaw aaaaaaaaaaaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aattc 2095 32 1838 DNA Homo sapiensSITE (1076) n equals a,t,g, or c 32 tgttcaccag tagctgggat tacaggcatgtatcactatg cctggctaat ttttgtattt 60 ttagtagaaa tggggttttg ccatgttggccaggctggtc tcaaacttct gacctcaagt 120 gatccacctg cctcggcctc ccaaagtgctgggattacag gtgtgagcca ccatgcctgg 180 ggcaaaagat attttcaaaa cattgtmaataacttctccc ccaaacccag acagggtctc 240 attctgttgc ccaggctgga gtggcaggggcaccatcgta gctcactgca gccttgaaca 300 ccggggctca agcaatcctc ccgcctcagcctgccaaagt gctgggatta cacacgtaag 360 ccagtgcact cagtcctaag taactttttaaataccaaag gtagaaaagg aagaagaggg 420 aaaaaaaaaa taagcccata tatggaaaaggaaaagacag cagataaata taggcaaata 480 gaggtggaaa atataatcac gtagaatttagtatagtaaa ggattatctc tgaaaaacaa 540 aaacagaaaa ctatcagagc caaataaagaaaaatggaaa tgactgggga aaaccactca 600 ctaatgagtt gaatgttcaa gagaaactgagaaagagtac tgcttatata aaaattatgt 660 gaaattaaac aaaaatgtag tttagtaatgaatggtgttt aagcacttat ggaatataaa 720 attatcacct gttaaataag aatgcatagtaaatggaatg gacaaagaat atgagtgaca 780 gataaaatca gtttttaaaa aattttattaaagttgatta agcctattag tgaaagaaag 840 caggccaggc acaatggctt gctcctgtaatgccaatact ctgggaggtc aaggcaggaa 900 gatcacctga gcccaggagt ttgagataagcctgggtaac acagtgagac tccatctcta 960 aaaaaattaa aaagtaaaaa aaaattagctggtcatggtg acacacacct gtsgkccyas 1020 skmctwkgga ggctgaggca agaggattacataagcccag gaagatgaag ctgcantgac 1080 ccatgattgt gccactgcac tccggcttgggtaacaaagt gagatcctat tttccatccc 1140 caaccagtcc ccccagaaaa ggccaggtgtggtagctcat gcctgtaatc ccagcacttt 1200 gggaggccga ggtgggagga ttgcttgagcccaggrgcyy ysagtascag tttaggcaac 1260 aaagtgaaac cctgtcttta caaaaggcaatacagtgaaa ccttgtcttt acaaaaagtg 1320 caaaaataag ctgggcatgt gtgccacaacacctgtaatt gcagctactc aggaggcaga 1380 gacaggagga ttgcttgagc ccagaggtcaagactgtaat gaaccatgat tgtgccattg 1440 cactccagtt taactgacag agtgagactctgtcttaaaa aaaaaattat tttgatatta 1500 agtgataagt ggctatttgc ctagtagcttcctaaaataa actagcataa aatgaaactt 1560 attttccaac ctatccctaa gcccttggaatttcagttct aataactaga atagttacat 1620 aaaaccagta aaaagttgtt taataagaatgtacacattt cccctactaa aatttattgc 1680 ttgtagtttc aaaataaaat cataaagttatctcaaagcc aagcaaaaaa attatttggt 1740 acaaagtagc aaactcgctg cattagaagaaaaggccatt tcttcacata tttgaataca 1800 ggcaccaaca catagttcca catgaaattatatttcgg 1838 33 782 DNA Homo sapiens 33 tacgagtttt ttttttttttttttgagaag gagtctcggg ctctgtcacc caggctggag 60 tgcagtggcg agactccgtttcaaaacaaa aacaaagcat caattcctga tcatgaccca 120 ctgtaacttc aagcaagctacaagaatcta tactagggtt cagacctttg aggctgacag 180 cgagctttga gtttgatgacagtacctaaa atatattaag tgtactcagg aactggccaa 240 gcatggggtg gggcttgtcaggaaactggt atttctttct tctatttgta gtgaataaga 300 tgctcaatag acgacttttactcctcgtca atggtcgcat aactgtctct ttttagacac 360 ttatgaaatt gtctgaacttcctcctctac ttctccaact cccagaagag tgaaggtaac 420 aaatgttatg tccaaaccacggtttgttcc cagaccctgg tttccaatgc ccacctcttt 480 tccaagaagt ccaaagagacgcccctcatc gcaaaggaag tgctaccgtg ctgcctcgat 540 gtcccccttg ggtgccatccctgaaacatc gaacctccca tacctcttct ccagccgtcc 600 ccctcatcct cgttccccgcctaccctctc ttcaacttca ttcattcatc caacattcgc 660 tgggggattt ctacattgacacgccccgga cagaagcctg gggtaaagat gatcaggaac 720 acgttccctc ccgctaagcggcttggcaga gtaagaggca tcccaaaact cgtgccgaat 780 tc 782 34 1560 DNA Homosapiens SITE (461) n equals a,t,g, or c 34 ggctttttct gacattggtgaaccccctag actacaatta atccctttgc tacagacacc 60 tgtagccctt gctgcctcctttttgttaag aggtcttata attttatgtt tgatgtccat 120 cttccccact tgattgaaatgcactattta tggaggagct atgtctgtat tgtttgttgc 180 tgtatcccta ttgtctagcatagtgcctga catacagtac aggctcaaga catatttgca 240 cattgattta tggaaaactgatactcaggt tctgaagaat aaataaatgc acctgaactg 300 tcaaagtgct aaaagcaggcaatccagaaa tgtctggagg taggaatcac agctgcaaga 360 ggcacttcct ggttaacctcgccctccgac ctctagttgg agccacccct ttggatccta 420 cttcagcctt tctggagtcagtggctcaca ggtttcctga nacaaagaga agaggcttga 480 gactattatt acatatnantcttctttaga agcaaagttg gttcgtggat tgaattttca 540 accttacagt accaattataaatcctgagg cattctatca gttaagacaa cttanaatat 600 ttgatcccat tcagaactttnncatttgtt ttaaagcagg aaaagtaaar gmagtcaatg 660 twmtaacyct tcttctttaaaatgtggatc atagtcctct tggggatgtt tgttcattta 720 atattaacat tttttaagcttgscatgtwt cgtgggtgta tctgtttggt ttcctttggt 780 aactgcattt tgccatgacccttgatacca gctctactgc tacagcccta ggctaggcca 840 ccgtcatctg tggcctggaccctttcagtc ctaactggtt gccgtgtctc ctttcttagg 900 ccccccaaca gttcatcttccatatccaca cacagtagcc cttaatgatg tttttaaagg 960 aatgagctat attaggatgatttctttgcc caaaaactcc ttcaatggtt ttccacttac 1020 tccagagacc caaaaatctaaggcattttc cctatgggcc ctggatggcc ccacattccc 1080 cctgaccccc gtctccagtgctgtcccctc ctgcttgctg tgcttccagc ccacactggc 1140 ttccttcctt accctcagggttccaccaat ctggatcttg tctcataaac tttgttcctc 1200 tgacttcttc tttttgaatgttcttttccc agaccttcac atggctcttt gctctcccct 1260 tctgagtctg aacacaaaggtcactgactt aaagaggctt tttcccacca tccagttgaa 1320 atcagcaccc tctctgtaactgtgtaccac attgtcttat tctttctcat aggtctgaaa 1380 ttgtcgtatt catttttaatgtattttttg cctttttgtc cctgctaaca tataagcttt 1440 ttgaggtcag agactttcttttcactgtag tattcccagt tcctaaaaca gggccctaca 1500 catattggat gtttaataaacatttattga ctaatacaaa tgaaaaaaaa aaaaaaaaaa 1560 35 1092 DNA Homosapiens 35 ggcacgtgtt gtggagtctc ctaagtgctt gctggacaca atttcttgtctatttttgct 60 gccttatgat tctccaaagg acatttcccc cacgggctct gaggacatctccgtggcttt 120 ccaaccccat gggggttaaa gggaaaaaaa aaaaaggaac gtttatggaaatgatgctag 180 ggttgttctc tcctctttgc cttgtcactg gaattgctga aggcagggctgaagatgctt 240 ctctacatga catctgcacc acccaacaca cacttacctt cacaccttcataccctgttg 300 gagggtcctg atgactacag ggcagtaaat tcagccccac aggagggccacagcagcccc 360 cagcctctag cctcctaccc tccttcttag gcaaccttga caggaaattttccctctgcc 420 ttctccttga tcccaacggt agctgcataa tagctgagct cacataatccctgtcgccag 480 tgctagagtg cccttagatg gaggtagccc aggtttgact tcctgaatccccagcagcag 540 gccttttctt tctagagctc tttgcaggaa gagaaagctt tggaccagctcatgctgggt 600 gtaatccttt gtggaagcct ccctgtttcc cttctctgat ctgccccggagattcctgtg 660 tgtcccagtc tctagggagg gaggcttagc tggagaggtt caagggcaggagaaagcagg 720 agaatgcaga ggccgcgggg agaggacaga aagtatatca tttataactaacctttagcc 780 tttagccact caaaaatatt tcctaatagc ctaagggttc ttggcaggtctttccccaca 840 tcagcaagaa atcttgggag ttgggaagag tcagaccttg ttccctgaacaagctttctg 900 ctttggccaa gagttgttag gagattaatg cctgtccctg aaaggcacaggttggagtgt 960 ttacttcttc ctctcctttc ctctctcccc ccttagagat cgtgacccttcctgcttgcc 1020 tccctggtgg gctctttcag gctggacaca gggtttaaaa aaaaaaaaaaaaaaaaaaaa 1080 aaaaaaactc ga 1092 36 1153 DNA Homo sapiens SITE (409) nequals a,t,g, or c 36 agactatcct caaggagctt acatatcagt aaataaattattaaaggtgg aaaatgtggt 60 aaaagagaca taatgtctcg gagagagaac aaatttctgctttaggagtg ttcttagtta 120 aggtaacatt agcttctata atacgcacac tcccaaatctcagtatttca acatgagttt 180 ctctcttgct catgtaaaga ctggtcaggg acccaggttgacagaggctc ttcagtacat 240 agcttccaag attgctgtgg gtgtgacatc cagccagaaatctggtgaag agagagcaat 300 grttacacag gaacttttaa tggaccaggc ctgggacagcgtatgtcact tccaccaaca 360 tcccactcac cagaatttsg tcacagggcc atagctatctgcagagaang ctgggaaatg 420 gaacttagct atgtgctcaa gaggaaaagt aaaacagttattgaataatt agtaataatt 480 agcaagtaac tacctagggg tcacagagga nctctcaggtagaatttaga cttaaagatg 540 atgggggagt gtgtggaaga gtggtgcaga atagggaaaggggggattga aggaagaaca 600 agctctagct tcacctgcat gggtagagcc cacagtgttggtagggacat gttagctttc 660 aacatcagct tcttaacagt attattcttt catcggaggaaattagtcta tttctgagga 720 aaaaaaaatc tgcaatacgt agcaatttac ttacttggatattgaatgtt aaagcagaga 780 gagactttgt cctcaaaacc ctcccatttc agaagtgaggagcctgggga ggtcatgctc 840 tctggatgtc acacagtgag tcactgtcaa agccagaatagaacccagac ctctcagttt 900 cccatwccag tgctctttct atgaggaaag tataagtttgagcattttta aaccttaatt 960 atgtagaaat aaccatgata ttttatcgta aattatttcantcatctcat tttaaatttt 1020 actccaaact aaaggaaaac ggtactgatt taaaacatctatcataattc aatatagccc 1080 atatttctnc tttaggaaaa attttttttt gtnttttatcctgaagaccc gtgccctctt 1140 cctgtgtctc atg 1153 37 985 DNA Homo sapiensSITE (633) n equals a,t,g, or c 37 ggcacgagca cacccccctg agaccagggagcatttattc aaggaaacac ttgtctttag 60 aggatgttga cgatgcccca aacttactgtagctgtcagg aaaattaggt gagctattta 120 gtatcattga gcttcatttt acagaaccagcatgttgtcc ttagacttcc ctctgatcct 180 tttaggtctc aacttacata ttgccctcttgagccttcta gttcccagac tgagttagga 240 accccaaccc atgctggact cagttagtcctttccacatt gtgctgtaat tggctatacc 300 ccatctgtcc ttcctgccag actaggagtctcctgcgggc cctaacgttc ccaatttccg 360 gtgtttggac tggtgctctg tagatgtttagggaatgaaa gggtaatgaa taaattaatg 420 aaacaaataa gaatcatata gtattagcagcactagataa aaggtgtaaa atcttaagtg 480 atccaccatc ttttaaataa ttcattcaaacgatatttca aatgcatatc acctccaaga 540 aatcgtttct gcatttcrrs tgasttctacgatgccwwrt gaatgarraa rsrrgracak 600 ggyrtggttc tggggggctg tgagagtaacggngcaatcc tngtcattgt cgtagttatc 660 tggccatcca gggcttctca ggttgccaaatgccttgtga tagtctctgt tgcaatctta 720 gaggaaaaat aggcataatt aatgtacgcattccaatatt tagtgctctt tcaacttaca 780 caggaatcat tcaaaaagat cattgcatttgataaacttt agaaaaaagt aatccagctt 840 cttcgtttac ctttgagata attgagaccctgagcagtga agtgaattgc tcaagcagca 900 cacacaggtg caacgcaaca gctcgttcacacaaacacgc ctacaggaag catgacacag 960 gaggcttctc ctttaaagac gaata 985 381122 DNA Homo sapiens SITE (380) n equals a,t,g, or c 38 agtgaaaagcagatgttaag tggcatatgt gtcttcagtc acctctgtgt gggttgttct 60 gtagtatagagggtgttcta aaaatgatct ttaggaatgg agtgaggctt gtttttgttt 120 ttgttttgttttacacttcc acacaatccc ttttcaattc cttgcaaact gctgagtatg 180 tactattttgccagcaaagg ctgagcctgt atgaacccag ccatgtgctt tgtctgtgca 240 tgtccccacacaggaagcac accagagaaa gcgatacttc agggtagatt gatttcatta 300 ggaacttcattatcaccagc ctcaaatggt tctggccagc agtctttttc tatctgtatg 360 attaacccttctctgccgcn nagcacctcc tcccaccacc tnttctcagt gttaacaggt 420 gatctagactcctactctca gagaaaattg aagccaacaa gtagaaagtc ttttttgcta 480 ccaaagacacaaacctatnt tgttntgcat ccatcctcac ccccgctggt gcttgttcaa 540 cacaggagtcctctctccac ctacccaaag cctgtcccct cctgctgtgc cctggatctt 600 atctctgtcattgccttaga aacctttctt gtatatattc atctttttcc ttcaatagat 660 ctttcttattggattttaag catgttgcag cctcttctgt taataaaaca acaatcaaca 720 aaaacactctcccttaactg catgctttat tccagctact accttatatc attcctttcc 780 ttcaaggccaaagtcctcag aagaggtggc aatatcctcc atcatttctt cacttcatac 840 tcattcttcaacacatacta atctagtctc ttaccccata attcattaaa acacttattc 900 ttgggtcatgggtgacttct gtatagctaa atccagtgga tatttttcag gcctcctctt 960 ccttacattttagtatttca ccctattggc cattcttttc ttcttgaaat actctctcct 1020 ttagcttttatgacactgta ctcctggttt ttctcccatt tcttgtctgc tcctgcttag 1080 ttccctctgtaaacttggcc tctttcacaa ggccagtaaa ca 1122 39 598 DNA Homo sapiens 39gaattcggca cgagctggct gcaaggtctg ttgggggagg gtcctcactt gacccttact 60ggggtcagtg tgggtcaagg gttaagtgtc accctcggcc cttgggagcc tcattgctga 120gggtctcagc gcttaccact ggtcctggcg tcacggactg tggagctggg ggcagcccgt 180ggtgggtttt atagcaagtg gtgagatgtg ggcgctgtgc tccaaaccag accccgttaa 240gtgccacatg gtcaacagtt tagtgtgcag aaatgaattt ccttctctta atttttcctt 300atttttccag cctgttgggg gaggtggagg tggtgaaatg ttagcagtga ccagttcatc 360ctgatctgct tgggaccttc cagttttagc actgaaagcc ccacagccca agaatccctt 420ggatatcaac cacggttcct ccttccagaa tgtcccaaga gccttagggc ctggagacac 480acaggtgggg gcctgagccc ctgtccccct cctccagatg gagcaggcag ggccccaggg 540ccccagggct cacggtgttc tggggtccac agtgtgctgt gcggccaggc tggtcttc 598 401129 DNA Homo sapiens SITE (1053) n equals a,t,g, or c 40 ggcacgagcttatttatttc tgctgtcctt tttcttatta ttctgcctat attatcctga 60 aaatatttagtcagttctgt tttgcccaca attagcatgg ctaggtcatt gatttcagca 120 ctcaggtcaggtatgtcccc aggaagggtc tcagtggttt ctttgcaggg atcacagcta 180 tgtcttttggtatctattgc aatcatgggt ttgcttctat tttgaatttg tctgtcttat 240 ctcttggacatcaaaagtgc ccttcagggt aggcatgcta cttgttttat atctgccacc 300 caatttcaactgtaaaatcc taatcacaag tggcaactag ataggttaaa atgatttctg 360 gaactttccttctggacatg taagatccta aaatcttacg agaatttcag tgagttgatt 420 ttgtctttaatattttttct taggaaaaag aagacccatt ttgaatctgt tcaactgaaa 480 acctcaagatccccaaatat atgaagagac agtgctgtag cccttgagac taatgaacaa 540 agaaacctgctctagtttta caggaccata ttttagggtc tgtcctcata cctgtcacat 600 tggtgatctcacagaggagg gccatgccgc tgaaaaggga aggagattga aacatttgat 660 tgccttatcacatggtcaag taccttgcca aataaaggaa agcaaatgat ttgggtctca 720 actgaagatgaagctcaact caggaagaga tttatctgta tatacacata actgaaaacc 780 aagtttaagcccaccaatgc actgctgatg catgccatat aattaatggg taactttgat 840 tctttatgacgtctacataa caagtgtgat ttggaaggca catgtgagca tatgcattat 900 gatccaatttatgttttttc tttgtttata ttttggggaa aattaaaatt tttttaaggt 960 atatttttcccattatttat tttcctgacc ttaaaacagc ttttctacta aaaaatggtg 1020 agcaatgaagacaataaatt tttcattttt ccnaaaaaaa aaaaaaaaaa aaaaaaaaaa 1080 aaaaaaaaaaaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaccc 1129 41 1158 DNA Homo sapiens41 ttaacccaaa tgggttggga tggcacgagg ggaaatggga ggggaagaga acagctgaca 60tcttgaggaa agctttgggg tagtggagag gtaagggggt catggtcagt ctgaactcaa 120caatagggct gaatgaattt accaaaggaa gctgccttat attatatgcc aggctgctgg 180ggaaagcctc aggtcctggc cagcccctgt tctcacaaga acatgcaggt taccacataa 240ataatggcat atgccttcca taggacgtca acctgactta aatctaccta taccctactc 300tctattcttt ggtttttggt tctcatccct gtggaaggaa atgggcctct tctggcatct 360catgctactc tgtgcttttc cttgggctcc aaattctagc tcataaagat gcaagttttg 420caatttccta taaatggtta agaaaagagc aagctgtcca gagagtgaga agtttgaaaa 480gagaggtgca taagagagaa atgatgtcca tttgagcccc accacggagg ttatgtggtc 540ccaaaaggaa tgatggccaa gcaattaatt tttcctccta gttcttagct tgcttctgca 600ttgattggct ttacacaact ggcatttagt ctgcattaca caaatagaca ctaatttatt 660tggaacaagc agcaaaatga gaactttatt tggtgcagtc agggctccat ttagttccct 720cactctgctt ctaatcaccc cttctcccag ccctcttcta tttgatagag gtctgtccct 780cagatcagca atgtcttagc ccctctcctc tcttccattc cttcctgttg gtactcattt 840cttctaactt ttaataaaca tttaggtata atacattaca gtaagtgcta tttagataca 900aacttaaaac atactatata ttttaaggat ctaagaatcc tttagagaag gcacatgact 960gaagtacctc agctgcgcag cctgtagcca gtttttttaa tgtaaaagta agaatgccag 1020ccttaaccta gccctgcaga taaaagctaa cttttattaa taccagccct gaataatggc 1080actaatccac actcttcctt agagtgatgc tggaaaaata aaatcagggg cttcaggatt 1140aaaaaaaaaa aaaaaaaa 1158 42 1767 DNA Homo sapiens SITE (765) n equalsa,t,g, or c 42 ccgggtcgac ccacgcgtcc gattgaacgg tttggggcat ccttcctaggaaaagaatgt 60 cagttaaggt ggggtctctt ctggttttgg tgtattttac cctgggcccagttgttgcag 120 aactggaggt gaccctgcct tctcattcct aacatttttc tctactaccacccggatttt 180 gaggcagacc cccaactcgt catggctcca gctgaagttt gaaatataacgtcccggact 240 tctagcctgt aggagctgca gatgtagtgg ggcagacatg gggagggtcagtggtgagcc 300 tatagaaaca tctctttccg caggaaaaga taaaggatgt gatgtgtgtagctcacctcc 360 aggctgaaat gcagactttc ctcatcttcc acagtaagca ggattcccttctgataacct 420 tgtcagaaat gttgtttttc aaagggcatg tatggtatct gtcactttcagtgatgattg 480 tgtcgtcagt tgatgtctct tgacctgaac tgagtatgcc tgtggaaggtcctcttagcc 540 ccctcacaga aataggaggg ggtgtcctcg ggctgtagct gtgcttcctctgaaggtcac 600 tggggaaaag ggataccaag ggccgttgtc cagcttatta tcccagctgctgcacaaagt 660 gtccaggaac tggtccttag agcttttgag ttttatcaga tcagtttgttccttgggttg 720 gccatcaaga tgggtctcaa tataaatgaa ggaatctgaa tagantccagttttatgtgt 780 ttctagagaa aatgctcaag tgttcttatg caagtcatgt tagatttatatgatgtgtga 840 aatctgctta caaggaaatt ttcatgattt gtgttagatt agcatttaattgtctgcttt 900 aacagatact taatttattt caaaaataag gaaaaataga ggaatcggtgtgaatgtttt 960 aagactgaga gatgatgatc ctttactttt cctgtaaaga agataatttttaaatctttc 1020 atatcctgta gagaaaacca acttttcctc tgtgatatag tacattatgtttgcactact 1080 ataatgtcaa gactgaaagt ataaaaaatg tacatataag attaattttnatatcttttt 1140 ttttaaaggg gtttgaggtg cctgcctggc tcattcagta aaacatacaactctcgatct 1200 tgggatcatg agttcaagcc ccacgttagg ggtagagttt actttaaaaataaataaaag 1260 gggttgagtc tattgcacta agctctacat gactaattta aagtggagagatgttgtgct 1320 agatttaaaa aaaataacta gttttcttaa tgtgtctttg tatgatcaacagcatgccat 1380 aagcaataca aaacaccaag ccttatactt acaagaaaaa aggttaacatactggtaaag 1440 ttctaaacat atcaaatgta cataagtgac aaaggtagga ttttaaggaaatgtcagtat 1500 atagagaagc tcagtactgc attaaggaac ttcttcagaa ctagngaagtattcctgtgt 1560 ttgaggagaa aacttagggg tttgagaagt tatatttttc tatttaaaagggttaaatta 1620 ttgcataatt tggaaaaggt tgctttgaat gtaggacnaa actgtttcaaagatttttgt 1680 ttgaaaagtt tatgtatttt tgtgccttaa tatttgttct gacttttaataaaatgcttt 1740 ctgnaaanaa aaaaaaaaaa aaaaaaa 1767 43 917 DNA Homosapiens 43 ccacgcgtcc gggctcaccc caggccgaga ccaggtggtc cgaccccatcgctcttcacc 60 aagggaagtc gccagcctcc atcgacacgt ggccagggcg acgcagtggtggtatgatcg 120 tcatcacctc tatcctctcc tccctggcca gcctcctgct cctggccttcctggcagcgt 180 ccaccgcacg cttgagccct cagtcacttc cagagacctg ataccggggttagtcagggc 240 aaccacctgg aggaagtggg ccaggagctg cttctagaag gaaggaaagggagagactgc 300 aggaggaccg gggacccagt gctgcctcct ctccccatcc agctccagcctgtggtggcc 360 ggaggaggcc ccggagcagc tgagaattgg ctccttcatg gggaagcgctacatgaccca 420 ccacatccca cccagcgaag ccgccaccct gcccgtgggc tgtgagcctggcctggaccc 480 cctccccagc ctcagcccct agcctggccc ttgtggctgg ggcgtgtgtggctgtggcca 540 gtgtgggggc aaggacgtgg tagttattcc cagcccctgc accctcctcctcacccctgc 600 caaagtccca ctgatgtagg acagatgtca gggttctaga cgtctttggtgcaaaaaggg 660 ggttttattc aagcacaggg acaggaccca tgggcaggga gagcggcaccggggtggtga 720 ggagtggccc gttatatata ctttcgagtt gggagggctt agagagagcgtaagtctcta 780 aggaattttg gaagcaaggt ctccagggtc ctgagggggc tagctgttgttaggaaaagg 840 tcatttatta ctgtttagta aaaactttca ccagaaaaaa aaaaaaaaaaaaaaaaaaaa 900 aaaaaaaaaa aaaaaaa 917 44 1987 DNA Homo sapiens SITE(1554) n equals a,t,g, or c 44 ggcacagttt ccagggaaag aagggcggggatgtcagggc tggagagtgc ccgtgtcctt 60 ctgtgtgcat tgggctcctt cctccttaattctctgcttt ccacttttag gctgaactcc 120 agtgcaccca gttagacttg gagcggaaactcaagttgaa tgaaaatgcc atctccaggc 180 tccaggctaa ccaaaagtct gttctggtgtcggtgtcaga ggtcaaagca gtggctgaaa 240 tgcagtttgg ggaactcctt gctgctgtgaggaaggccca ggccaatgtg atgctcttct 300 takakgagaa ggagcaagct gcgctgagccaggccaacgg tatcaaggcc cacctggagt 360 acaagagtgc cgagatggag aagagtaagcaggagctgga gacgatggcg gccatcagca 420 acactgtcca gttcttggag gagtactgcaagtttaagaa cactgaagac atcaccttcc 480 ctagtgttta catagggctg aaggataaactctcgggcat ccgcaaagtt atcacggaat 540 ccactgtaca cttaatccak ttkytggagaactataagaa aaagctccag gagttttcca 600 aggaagagga gtatgacatc agaactcaagtgtctgccrt tgttcagcgc aaatattgga 660 cttccaaacc tgagcccagc accagggaacagttcctcca atatgtgyat gacatcacgt 720 tcgacccgga cacagcacac aagtatctccggctgcagga ggagaaccgc aaggtcacca 780 acaccacgcc ctgggagcat ccctacccggacctccccag caggttcctg cactggcggc 840 aggtgctgtc ccagcagagt ctgtacctgcacaggtacta ttttgaggtg gagatcttcg 900 gggcaggcac ctatgttggc ctgacctgcaaaggcatcga ccrgaaaggg gaggagcgca 960 rcagttgcat ttccggaaac aacttctcctggagcctcca atggaacggg aaggagttca 1020 cggcctggta cagtgacatg gagaccccactcaaagctgg ccctttctgg agctcggggt 1080 ctatattgac ttcccaggag ggatcctttccttctatggc gtagagtatg attccatgac 1140 tctggttcac aagtttgcct gcaagttttcagaaccagtc tatgctgcct tctggctttc 1200 caagaaggaa aacgccatcc ggattgtagatctgggagag gaacccgaga agccagcacc 1260 gtccttggtg gggactgctc cctagactccaggagccata tcccagacct ttgccagcta 1320 cagtgatggg atttgcattt tagggtgatttgggggcaaa aataactgct gatggtagct 1380 ggcttttgaa atcctatggg gtctctgaatgaaaacattc tccagctgct ctcttttgct 1440 ccatatggtg ctgttctcta tgtgtttggcagtaattctt tttttttttt tttttttgag 1500 acggagtctc gcactgttgc ccaggctggagtgcagtggc gcgaatcttg gctncactgc 1560 caagtccgcc tcccgagttc caagccaattctcctgcctc agcctcccga gtagctggga 1620 ttacaggtgc ctgccaccac acccagctaacgttttgtat ttttagtaga gatggggttt 1680 caccatgttg gccaggcaga tctcaaacttctgacctcgt gatgcactca cctcggcctc 1740 ccaaagtgct gggattacag gcgtgagccactgcgccctg cctgtttgta gtaattttta 1800 ggcaccaaat ctccctcatc ttctagtgccattctcctct ctgttcaggt aaatgtcaca 1860 ctgtgcccag aatggatgac caggaaccttcaagagtggc tgaaaagatt gcagagttat 1920 cataataaat tgctaacttg cgtatwaaaaaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1980 aaaaaaa 1987 45 2053 DNA Homosapiens 45 acgctgggac ttgggcggtg gtggaggtgg taaccgtgat agtagcagctccggcgrcag 60 caacagcgac tacgagggat ggcggcggct gcagcaggaa ctgmarcatcccagaggttt 120 ttccagagct tctcggatgc cctaatcgac gaggaccccc aggcggcgttagargagctg 180 actaaggctt tggaacagaa accagatgat gcacagtatt attgtcaaagagcttattgt 240 cacattcttc ttgggaatta ctgtgttgct gttgctgatg caaagaagtctctagaactc 300 aatccaaata attccactgc tatgctgaga aaaggaatat gtgaataccatgaaaaaaac 360 tatgctgctg ccctagaaac ttttacagaa ggacaaaaat tagatagtgcagatgctaat 420 ttcagtgtct ggattaaaag gtgtcaagaa gctcagaatg gctcagaatctgaggtggta 480 agtccaaagt tttcattctt catgttttta ttattttaaa tttcagctaccaaatatatt 540 tgagacaaga ctcaggatga gctgtctgat atttaaatat taagcaattccatttaagtg 600 ctggttcctc taggcactga aataaaatca ttttttgata aatatagaagtttccagtca 660 tgaaaattat tggcctattt taatgaattt agtgtgtggt taaagttgatttcgtgtgtt 720 ttaatatggt catgatgatc atttatcttt tccgttacta aaaccttattgcatttattt 780 aggttcaaca gtttgaatca cttgtagggc tttttatgat aggctaagacaaaagttaaa 840 gaaaattgga aattgacagg gtcttgctct gtcatgcagg ctggagtgcagtggtgccat 900 catagtgcac ttgagcttca aactcctggg ctcaagcaat cttcccacctcagccttcca 960 agtagctggg actacaggtg tacaccacca agcctggcta attactctgtttctttaaaa 1020 cgatttttaa aacaatgtta ttttagttta ggaagttgct gaatcttagaactggccatt 1080 ttatataagc aaccttttct aatcatgcct ttagaagttt tctgttatttaaagttctgt 1140 tattttagag caaaaatctt ttatgaaatt caatctaaga ttttttaaatgctgagcatt 1200 ctaatttttt tccgaaaact agtggtattt aacaattaca gttactatgtctttggaagg 1260 aaaattttca tgtagttatt ttatatcaaa ataactgcag tgttgggtaaattaataata 1320 catgcatttt aataatacag ttgctaaact gacttgtaaa aatctttctctttcaactta 1380 ccaaaatcaa tctgcatccc agtggactca tcagtcaaaa atcaagtatgactggtatca 1440 aacagaatct caagtagtca ttacacttat gatcaagaat gttcagaagaatgatgtaaa 1500 tgtggaattt tcagaaaaag agttgtctgc tttggttaaa cttccttctggagaggatta 1560 caatttgaaa ctggaacttc ttcatcctat aataccagaa cagagcacgtttaaagtact 1620 ttcaacaaag attgaaatta aactgaaaaa gccagaggct gtgagatgggaaaagctaga 1680 ggggcaagga gatgtgccta cgccaaaaca attcgtagca gatgtaaagaacctatatcc 1740 atcatcatct ccttatacaa gaaattggga taaattggtt ggtgagatcaaagaagaaga 1800 aaagaatgaa aagttggagg gagatgcagc tttaaacaga ttatttcagcagatctattc 1860 agatggttct gatgaagtga aacgtgccat gaacaaatcc tttatggagtcgggtggtac 1920 agttttgagt accaactggt ctgatgtagg taaaaggaaa gttgaaatcaatcctcctga 1980 tgatatggaa tggaaaaagt actaaataaa ttaatttgct ctcaaaaaaaaaaaaaaaaa 2040 aaaaaaaact cga 2053 46 1272 DNA Homo sapiens SITE (1264)n equals a,t,g, or c 46 aggctgctac actaatagga tgtagcaaag ggcggaggaggagatccaga agcaaacaca 60 agcaatgcaa gaactccaca gagtggagct ggagagagagaaagcgcgga taagagagga 120 gtatgaagag aaaatcagaa agctggaaga taaagtggagcaggaaaaga gaaagaagca 180 aatggagaaa gaaactagca gaacaggagg ctcactatgctgtaaggcag caaagggcaa 240 gaacggaagt ggagagtaag gatgggatac ttgaattaatcatgacagcg ttacagattg 300 cttcctttat tttgttacgt ctgttcgcgg aagattaaacttaatgaaaa tctgtttgta 360 ttttctgcat attctctggc aaccttgccc catacttacttatttagcat agtcgagtgc 420 tctagtttct gtctctcagg cactcgtaac taaggaccaccattggccat tggtagatgt 480 ttgattgact taacaagaga gggacaaatt ttcaatttgtgaaactccaa agcagaaagt 540 attggtgctt gctaccttgt gaattcttcc ttagacatgcagagaaaatg tatgcaagag 600 accaaaaaga tggctccaag ctatgtcatg ttacctgtaataaaatcttt tcttctagat 660 tctttctatg ttggcagata atctcccctt gtagcttccactcacttatt cttgcattca 720 gagtcacaat gatcatctta cccatgtggt ttttgagaaagaaagatcaa ttctttgttt 780 gcagtaggta atcttagaga tggagatgat tgtagaattattcctagatg agtgtcaatt 840 tatttaattc cattgtcata taaggagtca aattgtttcttatcatttgt tcattgaaga 900 acagagacct gtctggaaaa tcgatctcta caaattcaattaaataatga tccccaaatg 960 sykmaaaagt gaaatacagc aattcaacag ataatagagcaatgtttagt atattcagct 1020 gtatctgtag aaactctttg acgaacctca atttaaccaatttgatgaat acccagttct 1080 cttcttttct agagaaagat agttgcaacc tcacctccctcactcaacac tttgaatact 1140 tattgtttgg caggtcatcc acacacttct gcccccactgcattgaattt tttgcttatg 1200 ttgtttataa taaaactttt caattatctc ataaaaaaaaaaaaaaaaaa agggggggcc 1260 cggnacccaa tt 1272 47 773 DNA Homo sapiensSITE (459) n equals a,t,g, or c 47 cggcacgagc ttttgcccat aggataagtacaaactagat ctggttactg cctgccccac 60 cagcctcagt atctctcaca actaggactaactttttctt ctgacaacta taaaatattt 120 cccttgcctt ctcaagtttg ctcaaggtcaagttatgcct tttgcctgga atgacttgac 180 ttctcttttg ttttacttag ctggctgcttttcatcttgt aggttaggtc aagggactcc 240 aggaagtctt ccctggacaa gtaatgaagagggcataatc caagggccaa ctcccatgtt 300 ttggaacctg actccatttt caggcacgtaatattgtcaa attcctttta aaagcacctg 360 tctgtctgtt aacgttggtg cagatactgctattcccctc ctccatacca ttgctgatgg 420 ttactgaggg tatgggaagg gccgactagtccagctgtnc acaaacagcc cttaatgtca 480 aactgaatac tgccaacgta gtnccagtttctgtatctaa agactcagct tggagtcact 540 tgtctggact aaaaaagtac ccctccttgtctggtttgtg actttctgta ctctgatgcc 600 cccagctttc tgccttctag aaatttgtcagaatttccaa aattcttggg ccttccttct 660 tgctctatat atggttttgg attcattccttttaaaaaat atttactgtc atttcagtag 720 aattttgaca caataaatat aagcacatcaaaaaaaaaaa aaaaaaactc gga 773 48 2119 DNA Homo sapiens SITE (1424) nequals a,t,g, or c 48 wgcaagcttt gggagttgtt cgctgtccct gccctgctctgctagggaga gaacgccaga 60 gggaggcggc tggcccggcg gcaggctctc agaaccgctaccggcgatgc tactgctgtg 120 ggtgtcggtg gtcgcagcct tggcgctggc ggtactggcccccggagcag gggagcagag 180 gcggagagca gccaaagcgc ccaatgtggt gctggtcgtgagcgactcct acgatggaag 240 gttaacattt catccaggaa gtcaggtagt gaaacttccttttatcaact ttatgaagac 300 acgtgggact tcctttctga atgcctacac aaactctccaatttgttgcc catcacgcgc 360 agcaatgtgg agtggcctct tcactcactt aacagaatcttggaataatt ttaagggtct 420 agatccaaat tatacaacat ggatggatgt catggagaggcatggctacc gaacacaaaa 480 atttgggaaa ctggactata cttcaggaca tcactccattagtaatcgtg tggaagcgtg 540 gacaagagat gttgctttct tactcagaca agaaggcaggcccatggtta atcttatccg 600 taacaggact aaagtcagag tgatggaaag ggattggcagaatacagaca aagcagtaaa 660 ctggttaaga aaggaagcaa ttaattacac tgaaccatttgttatttact tgggattaaa 720 tttaccacac ccttaccctt caccatcttc tggagaaaattttggatctt caacatttca 780 cacatctctt tattggcttg aaaaagtgtc tcatgatgccatcaaaatcc caaagtggtc 840 acctttgtca gaaatgcacc ctgtagatta ttactcttcttatacaaaaa actgcactgg 900 aagatttacw aaaaaagaaa ttaakaatat tagagcattttattatgcta tgtgtgctga 960 gacagatgcc atgcttggtg aaattatttt ggcccttcatcaattagatc ttcttcagaa 1020 aactattgtc atatactcct cagaccatgg agagctggccatggaacatc gacagtttta 1080 taaaatgagc atgtacgagg ctagtgcaca tgttccgcttttgatgatgg gaccaggaat 1140 taaagccggc ctacaagtat caaatgtggt ttctcttgtggatatttacc ctaccatgct 1200 tgatattgct ggaattcctc tgcctcagaa cctgagtggatactcttcgt tgccgttatc 1260 atcagaaaca tttaagaatg aacataaagt caaaaacctgcatccaccct ggattactga 1320 gtgaattacc atggatgtaa tgtgaatgcc tccacctacatgcttcgaac taaccacttg 1380 gaaatatata gcctattcgg atgttgcatc aatgttgcctcaantctttg atctttcntc 1440 ggatccagat gaattaacaa atgttgctgt aaaatttcccagaaattact tattctttgg 1500 atcagaagct tcattccatt ataaactacc ctaaagtttctgcttctgtc caccagtata 1560 ataaagagca gtttatcaag tggaaacaaa gtataggacagaattattca aacgttatag 1620 caaattttag gtggcaccaa gactggcaga aggaaccaaggaagtatgaa aatgcaattg 1680 atcagtggct taaaacccat atgaatccaa gagcagtttgaacaaaaagt ttaaaaatag 1740 tgttctagag atacatataa atatattaca agatcataattatgtatttt aaatgaaaca 1800 gttttaataa ttaccaagtt ttggccgggc acagtggctcacacctgtaa tcccaggact 1860 ttgggaggct gaggaaagca gatcacaagg tcaagagattgagaccatcc tggccaacat 1920 ggtgaaaccc tgtctctact aaaaatacaa aaattagctgggcgcggtgg tgcacaccta 1980 tagtctcagc tactcagagg ctgaggcagg aggatcgcttgaacccggga ggcagcagtt 2040 gcagtgagct gagattgcgc cactgtactc cagcctggcaacagagtgag actgtgtcgc 2100 aaaaaaaaaa aaaaaaaaa 2119 49 1188 DNA Homosapiens SITE (577) n equals a,t,g, or c 49 gaattcggca cgagtaattttgtattttta gtagagacag ggtttctccg tgttggtcag 60 actggtctcg aactcccgacctcaggtgat ctgcccacct cggcctccca aagtgctggg 120 attacaggcg tgagccaccgagcctagccc tgtttaggct ttttatagcc tatgttctta 180 tgagcagtaa acattatgaatggtttagtt agacctgttg aattgaattc acttcttctg 240 cctgtggtca ggtatcaggtagcacagcca cagaagttac tgaatgtctt tgttggtgga 300 ctttaggaaa gtggtttaatttatgtggta ttcctatctg ggaattgcaa cagtattgtt 360 agattgcatt ttgtcacagggaggaaatta cctggtaact ccctgattag gaacaaaatg 420 aagcttcccc tttttacaaatcctggctaa cattccattt ggatctcttc tgttgaacac 480 ctctctctct cccctccctcctcactccat tttctcagtt attttattgt ttactattgg 540 aagtcacctc ccaactcaggatacttgtta gtccatntta ggaaaaatat caccattctt 600 tcactattat tctctgttgaagttgaagaa cagaatatta ctttttttct ttccattatt 660 ggttacacca gctagttagagacttggggt aatactgtgg gcatgggttg gatcctgata 720 tctgtgtcag ttagtgagagttggttctat gaccctagag ctctttgtgt ccttcaaacg 780 agggtgctga aacaagacgaacatagaact gtctatacca agcaaaaaac tcctgaaagc 840 acatgcccac tgcaggtgaattggtagcat agtgtggaga taagtgggca gtgcttggtc 900 ctgtttctgc ctcctagagagtacctctca gcatccaggg atgctttagt aactcttagt 960 taaaacgaaa tgaactataattaattacct tttttttggg ggggacacag agagtttcca 1020 cngcatttac catgcttttttttttttttt gnaaaggaaa tatgatagga tattaagatt 1080 gacagagctg gggatgggttggaggctgaa ttatgatgtg tgtatttctt tatgcttgga 1140 ttatttcata attaaaaaccaaacatataa aaaaaaaaaa gaaaaaaa 1188 50 478 DNA Homo sapiens 50ttttttagca tttcacgcta tttattcccc aaaaccttct gccatagaag acagccacca 60tacagattgg aaaatgtgga cgaggagaaa aggggtgtat ggtaagcaaa ataaattgta 120ttttccatcc ttggggagga taaaggaact ctttgcactg ctataatgaa cagcccccaa 180atgccagtgg tttaattcag tggagttcag acctcattcc tatatcattg cagtgtggat 240gctcctggat gaaggctctt gtaggtaact ctcctccagt cggtgattca gggacccagc 300ctccttctgc cttgcggctt tgccttttaa aggtcctcag ggtgctctcc atgtatcttg 360ccaatgggga acgagtgtgg aggactcaca agcgggtcyc acatcacgtc ctccggggct 420aatacacatc ccttctcccc acactctgtt ggtcagaagt cactgcttgg cgccctgc 478 511333 DNA Homo sapiens SITE (485) n equals a,t,g, or c 51 agctggtaccaaagcaagtt tttcactgag ctctcatgaa agatcctcag tctcttgtgg 60 atttagaatcctgcagcagc ccaccatcta agagcaagar ccaaagatgt ttgtcttgct 120 ctatgttacaagttttgcca tttgtgccag tggacaaccc cggggtaatc agttgaaagg 180 agagaactactcccccaggt atatctgcag cattcctggc ttgcctggac ctccagggcc 240 ccctggagcaaatggttccc ctgggcccca tggtcgcatc ggccttccag gaagagatgg 300 tagagacggcaggaaaggag agaaaggtga aaagggaact gcaggtttga gaggtaagac 360 tggaccgctaggtcttgccg gtgagaaagg ggaccaagga gagactggga agaaaggacc 420 cataggaccagagggagaga aaggagaagt aggtccaatt ggtcctcctg gaccaaaggg 480 agacnnatgatanctntggg acccggggct gcctggagtt tgcagatgtg gaagcatcgt 540 gctcaaatccgccttttctg ttggcatcac aaccagctac ccagaanaaa gactacctat 600 tatatttaacaaggtcctcc ttccacgagg ganagcacta caaccctgcc acaggggaag 660 ttcatctgtgctttcccagg ggatctatta cttttcttat gatatcacat tggctaataa 720 gcatctggcaatcggactgg tacacaatgg gcaataccgg ataaagacct tcgacgccaa 780 cacaggaaaccatgatgtgg cttcggggtc cacagtcatc tatctgcagc cagaagatga 840 agtctggctggagattttct tcacagacca gaatggcctc ttctcagacc caggttgggc 900 agacagcttattctccgggt ttctcttata cgttgacaca gattacctag attccatatc 960 agaagatgatgaattgtgat caggaccaag atccctgtgg taaacactct gattgaatct 1020 ggggttccagaaggtggaac aagcaggaat gggatccaaa gagactccca ctcagattct 1080 aaagcatttaaagacaattc tagcagaatt tatcaaaaca agatgaaaca cagaaaagtt 1140 gaaaccacaacaaaatgaat tctattaaag aatagcccca gatataaatt ctcttgaaag 1200 caatgttcataaatatttaa gcaaattaaa gacaatgtta acaaattttc tattaaatgc 1260 cctgagtgataaaaccagtt ggcaataata ttgccttatt aaatcttcaa aaaataaaaa 1320 aaattaaaanaaa 1333 52 1255 DNA Homo sapiens SITE (541) n equals a,t,g, or c 52gaattcggca cgagcacatt taataatcta attcacacac acacacacac gtgaaatcat 60tcttgagaat gaaatttatc atgcttttac ttcttccttc aatcttccca actactgttg 120aaatgatctg agattttaga tctacattat tgttactttt taacattatg tatcttctgt 180ttcaagaagg cttttgatgt ttgagttaag tttcataagc ttttaaacaa gcatttagac 240atttacacct gcttaactga tttcattgat cacttttatt tcatttgcac tgtatatccc 300cattatttca actcatttca cagttgtctt tggtacttct tttagtactt ttttaaggaa 360cagatgggtg atacagtatt atatgttctt gccttcctga agatacttgt gttcaataga 420gcgtaacatt tttttcccac agtgactttt ccctcagaat actaaagtca cagaaagtta 480tcacatcaac ttaatgttgc ccaagagaag tccaaactct ttgcgcttct tttgtaggtt 540nntttgggtt atctccccac aatgatgttt atagattctt tattctttct tcttggaaca 600aagaaatttc attgggatat gtttttaaaa atagatctct ttttattatt tttgcatggt 660actagatgag acattttagt gcatagatgc aagtcttttt tcaactctgg gaattttact 720tctatggaat ttttttttct ttccctaata ttttttcact ctttttctta tcctttagaa 780atttttatgt tgatccccta gatctgctct ctgttctgac tagtttttgc tcattatatc 840tttttatcct tttcccttag aatcagtact tcttgaaata aactgcttct atgattctga 900ggtatagcca aattggggaa gccctcttgt gaagggtcag cagtgtttac ctggaagaag 960aacccatttc agttgtgctt cttgctgttt ggctgcctga ttcaatcagt ggcagaaaat 1020catattaaat atatttagag tactcccttt aaaagratta cctctctttg aaattcagta 1080aatttacatt gagratattt gacaaatttg tatatacatt tgcaggcaat aatttttatg 1140agctgatctg ccatgnttaa angttttcct ttgtaaacca tttggtgtgg gtatttttta 1200aatttcctca gtatgatccc agngggcatt aactgtccaa aaaaaaaaaa aaaaa 1255 531140 DNA Homo sapiens 53 ctaggagcct cctaatgcag tgttctgcac agtcctggggactgactgac tgaatcacac 60 ctctggggct gggggctgct gacatgtgtg cctttccttggctgcttctt ctcctgctgc 120 tccaggargg cagccaaagg agactctgga gatggtgtggatccgaggaa gtggttgcgg 180 tccttcagga gtccatcagc ctccccctgg aaataccaccagatgaagag gttgagaaca 240 tcatctggtc ctctcacaaa agtcttgcca ctgtggtgccagggaaagag ggacatccag 300 ctaccatcat ggtgaccaat ccacactacc agggccaagtgagcttcctg gaccccarct 360 attccctgca tatcagcaat ctgagctggg aggattcagggctttaccaa gctcaagtca 420 acctgagaac atcccagatc tctaccatgc agcagtacaatctatgtgtc taccgatggc 480 tgtcagagdc cccasatcac tgtgaacttt gagagttctggggaaggtgc ctgcagtatg 540 tccctggtgt gctctgtgga graaggcagg catggatatgacctacagct ggctctcccg 600 gggggatagc acttatacat tccatgaagg ccctgtcctcagcacatcct ggaggccggg 660 ggacagtgcc ctctcctaca cctgcagagc caacaaccccatcagcaacg tcagttcttg 720 ccccatccct gatgggccct tctatgcaga tcctaactatgcttctgaga agccttcaac 780 agccttctgc ctcctggcca agggattgct catcttcttgctcttggtaa ttctggccat 840 gggactctgg gtcatccgag tccagaaaag acacaaaatgccaaggatga agaaactcat 900 gagaaacaga atgaaattga ggaaggaggc aaagcctggctccagccctg cctgactgct 960 ccttgggaac cccagtcctg agcttggttt cttcccagcacccagagaat ccttcctcag 1020 ctctcttctt tccaggggaa ggaggtgctc aggggtgggtatccagagag ccatacttct 1080 gagggaagac tggctggcaa taaagtcaaa ttaagtgaccaccaaaaaaa aaaaaaaaaa 1140 54 1220 DNA Homo sapiens SITE (1197) n equalsa,t,g, or c 54 ccacgcgtcc gcaaataggt acctaaggca tgtgatttta tttttaaataacaaaaaata 60 acccaagttt cttgcttctc caaagtattc ttctcatagc ttataaaagaaagtccacat 120 tgaatagcat ggtctgggaa cattccttct ttattgtgtt tatttgaacatgatatgagt 180 ttccaagatg aaatgatcaa aaaagataag taccacaaga aagtttttttgtttggttgg 240 tttttttgtt tgtttgtttt tttcttgaga ctgagtctct ccctgttgcccaagttggag 300 tgcaatcttg gctcactgca gcctccacct ccccggttcc agcgattctcctgcctcagc 360 ctcttgaata gctgggatta caggcgcccg ccaccacacc tggctaatttttgtgttgtt 420 agtagaggcg gggtttcatc atgttggcca ggctggtctc gaactcctgatctcatgatc 480 cgtctgcctc ggcctcccag agtgctggga ttacaggcat gagccactgcgcccggccaa 540 gaaagtatgt ttttagaggt gtgtgtaagt gcatttgtat tacctatgaacaaaattacc 600 tgactcttgt cccaggaaag ctgtttcgca ttttcgcttt ttgattggtattatccagtt 660 ctatgtagtt catattattg ttctgtctga ctctcagaaa ttacttcttcacgccagtgt 720 cttgttgcat gactttgatg tcacctatag gaatacacct cactgcacgtaagtgggtat 780 cttactgtat aaaaggtcta catggcttta ggttttagga caaatgtgtagatttataga 840 ccatttctgt tggccaggac acagattttg agagctgtgt gtatatatatataatcatgt 900 ttgtattttt ttcctgaaag ttatcaattg cttttgttta aaacagtttgttttagaggt 960 ggggtgggga tgtatataac gaggaaaagt tatatgtact ttaaagtatgtcaagttctt 1020 actagtttcc tgtactgaag gttcaatttt ttttatataa gtttacttttcacctgctct 1080 attctttgtg gggaaaaaat gcatctagaa aaacatagtt taaatactgtatataagata 1140 atgaaagtta gtaatgtcca ttatttaata aagtttgtaa agtacaaggtaaaaaanaaa 1200 aaaaaaanna aaaaaaaagg 1220 55 694 DNA Homo sapiens SITE(621) n equals a,t,g, or c 55 ataactggag agacatcaaa ctcatgctgagaacaactag aagagttaga attgaagaaa 60 aaggatttca ttaagatatt agagagtgttcaaggcaact ggaggcagaa cgargattct 120 ggaaaggggc cacagagaag ttgtctgcattcaaaagagc attctattaa agctacctta 180 atttggcgct tatttttctt aatcatgtttctgacaatca tagtgtgtgg aatggttgct 240 gctttaagyg caataagagc taactgccatcaagagccat cagtatgtct tcaagctgca 300 tgcccagaaa gctggattgg ttttcaaagaaagtgtttct atttttctga tgacaccaag 360 aactggacat caagtcagag gttttgtgactcacaagatg ctgatcttgc tcaggttgaa 420 agmttccagg aactgktaag aaaatagttctggccagaat caaagattca gccctacaag 480 gatatgtttt cctgtgaaat tatctaagagaatttcctgt tgagatataa aggcccatct 540 gatcactgga ttgggctgas caragaacaaggccaaccat ggaaatggat aaatggtact 600 gaatggacaa gacagtaagt nctaaaaatctggcagtaat atttgtattt naatttactt 660 tgcattaaat ctgaagtgtt ctctagttacatgc 694 56 988 DNA Homo sapiens 56 cggcacgagc cagaccctat gatgtgtccactctggaggc tcctcatctt cctcgggttg 60 ctggccttgc ccttggcacc acacaagcagccttggcctg gcctggccca agcccacaga 120 gacaacaaat ccaccctggc aagaattattgctcagggcc tcataaagca caacgcagaa 180 agccgaattc agaacatcca ctttggggacagactgaatg cctcagcaca agtggcccca 240 gggctggtgg gctggctaat cagcggcaggaaacaccagc agcagcaaga gagcagcatc 300 aacatcacca acattcagct ggactgtggtgggatccaga tatcattcca taaggagtgg 360 ttctcggcaa atatctcact tgaatttgaccttgaattga gaccgtcctt cgataacaac 420 atcataaaga tgtgtgcaca tatgagcatcgttgtggagt tctggctgga gaaagacgag 480 tttggccgga gggatctggt gataggcaaatgcgatgcag agcccagcag tgtccatgtg 540 gccatcctca ctgaggctat cccaccaaagatgaatcagt ttctctacaa cctcaaagag 600 aatctgcaaa aagttctccc acacatggtagaaagtcagc ccctggcctg atccttctct 660 ctgtgctgat ggtccaggta tgtcctctgatcggtgaaat cctcgggcag ctggatgtga 720 aactgttgaa aagcctcata gaacaggaggctgctcatga accaacccac catgaaacca 780 gccaaccctc tgcatgccag gctggagagtcccccagctg acttctgctg atcagaagga 840 aagtccacat cttgcaacct taagtctcccttagagtggg gcttctgcta ccctaaaaac 900 tttaccccag gctctgtgga cataccatcctctcctacaa taaactctag ctctgaaggg 960 tgaaaaaaaa aaaaaaaaaa cggcacga 98857 1500 DNA Homo sapiens SITE (71) n equals a,t,g, or c 57 gcctgaagggtcgtgaggct ggggcgggac ccggcaccgc tggggcgcca ggccgtgagg 60 acgccaatggnangcakcgt ggacgaggag gcrctcacca gctgtacctg tgggtagaca 120 acatccctctgtcccggccc aagcgaaacc tctcccggga ctttagcgat ggagtccttg 180 ttgcagaggtcatcaagttt tacttcccca agatggtgga gatgcacaat tatgtcggca 240 cgagctctctccagcagaag ctcagcaact ggggtcatct gaacaggaag gtactgaaga 300 ggctgaacttttcagtaccg gatgacgtga tgcgcaagat cgcgcagtgc gccccaggcg 360 tggtggagctggtgctcatc ccgctgaggc agcgcctgga ggagaggcag aggcgcagga 420 agcagggcgccggctcctta caggagctgg ctccccagga tggcagtggc tacatggatg 480 tgggtgtatcccagaaggcc cgaggtgaar gtgtcccgga cccccaggga gggggtcagc 540 tcagctgggaccggccgccg gcgcctcggc ctccagcgta taaccgggcg ttgcagggcg 600 accccagcttcgtcctccag atcgctgaaa aggagcagga gctgttggcc tctcaagaga 660 ccgtgcaggtcctgcagatg aaggtaaggc gcctggagca cctgctccag ctcaagaatg 720 tgcggatcgaaaacctctcc cggcggctcc agcangcgga rcgtaagcag cggtgagcgg 780 cggcccgggccgcgcgggga cgcccgggta cccgccagag ccccgacgcc gcgccggacc 840 cacccaccgatggatagacc attgggaggg cggagcccgc tgctctcacg agcctgctgg 900 ggcccgagtgccctccttcc ttgggatggg tgagcgtgga ggagatggga caggaactct 960 aggagcgcaggcccgggact gagccgcctc ctaccactcc ggagatccgg gtcaggagaa 1020 tggaccgctttccagagccc agaagccacg tgcagagacc tagcctgtcc cccaaagcag 1080 tgtccaacaccttgggcccg gccttgcatc tcccggcgct gggccttggg gggcggtccc 1140 ttggctctgtccacaccccc agaatcaggt ccccgcccag ctccgaggac ggcggcgtct 1200 ccatccaggctagttcccca tgccctcagc catgggggaa tctgtcccgg gccgctgagg 1260 ggctcccctgcccctcctgg gagcttacct gggacccacc tcggcgacgg agaccgcagc 1320 agctggagaggaaggggtga ggcgtgggat cgccaggagt agggaggaca tcgacgatgt 1380 gcccgtagcagtcgcccctc cctcctcgcg cacggggtac tgaggcggaa ggtttgaagg 1440 ttacggctcagggctgcccc attaaagtca gtgttgtgtt ctaaaaaaaa aaaaaaaaaa 1500 58 1391 DNAHomo sapiens 58 ggtaaatacc aaggtaatta aatttttaag ttctgagtat tagaggtaatggttactgta 60 gctcctaaaa tgcacatcac atctctggta ggtgctggaa ccctcatggtactgctgctt 120 ttaattttgc ttttggaatg tttctttgta gctgaagctt tagtgatgagaagttagaaa 180 tactctcatt gacctttagt gttttgtcct gttgatatat atcaagttcgcttagtttga 240 cattgtttga acttatttcc ctaagcaaaa aacagccaga aagaagaaaatccagaacat 300 gtagaaattc agaagatgat ggattccctc ttcttaaaat tggatgccctctcaaacttc 360 cactttatcc ctaaaccgcc tgtaccagag attaaagttg tgtcaaatctgccagccata 420 accatggagg aagtagcccc agtgagtgtt agtgatgcag ctctcctggccccagaggag 480 atcaaggaga aaaataaagc tggagatata aaaacagctg ctgaaaaaacagctacagac 540 aagaaacgag agcgaaggaa aaagaaatat caaaagcgta tgaaaataaaagagaaggag 600 aagcggagaa aactgcttga aaagagcagt gtagatcaag cagggaaatacagcaaaaca 660 gtagcttcgg agaagttaaa acagctgacc aaaactggca aagcttccttcataaaggta 720 aggacaaggg aaagaaaact gctcaagggg acctttgtgg gggaagtggatagcaagtgc 780 tgggtgactg gaatgtctga gccagctgac agcccacctg tgggatagagatgcatgatg 840 ctgactggct ggaatcgcaa cctttaatgt tctagaattt ttcacgtagggtcctcacaa 900 taacctgggt cctggcagca gcttgtcttc cactcctttc tctcttagattataagaaca 960 ttgtagcagt gcagaatacg tctatgctaa ctgattccag ttttctgtaattctagtccc 1020 tttttcatat ttatggttgc atacattgtt gtaatggtga tgtactatttttggcttttt 1080 tcacttataa gtacatttta cagcataagc atgtggtgtt tttaattgcaggatgaaggt 1140 aaagacaagg ccttaaagtc ctctcaagca ttcttttcta aattacaagatcaagtaaaa 1200 atgcaaatca atgatgcaaa gaaaacagaa aagaaaaaga agaaaagacaggatatttct 1260 gttcataaat taaagctgta atatattttg aatataatgt aaatattaatgtgtaagctt 1320 atattgtgtc attgttctgt tttataataa aattcttgag aaccttcaaaaaaaaaaaaa 1380 aaaaaactcg a 1391 59 1579 DNA Homo sapiens 59 ggcacgaggcagcgcaggga gctgtctgca gaggccaggg tgcgcctgcc acgaatcccc 60 aggcaccggtggccgccgcg gcccgagtag ctcggcgggt aaacatggcc gcactgacga 120 cggttgtggtagcggctgcg gccaccgcgg tagccggggc tgtggcaggg gcgggcgcgg 180 ccaccgggaccggcgtggga gcgacgccag cgcctcaaca gagtgatggc tgttttagta 240 cttcaggtggaattcgtcct tttcatcttc agaactggaa gcagaaagtt aatcagacta 300 agaaagcagaatttgtacgc acagcagaaa aatttaaaaa tcaagtaatt aacatggaaa 360 aagataaacacagtcatttc tacaaccaaa aaagtgactt cagatttgag catagtatgc 420 tagaagaattggaaaataaa ttgattcaca gcaggaaaac agaaagagca aaattccagc 480 aacaattggccaaaatacat aataatgtaa agaaacttca gcatcaatta aaagatgtga 540 agcctacacctgattttgtt gagaagctca gagaaatgat ggaagaaatt gaaaatgcaa 600 ttaacacttttaaagaagag cagaggttga tatatgaaga gctaattaaa gaagagaaga 660 caactaataatgagttgagt gccatatcaa gaaaaattga cacatgggct ttgggtaatt 720 cagaaacagagaaagctttc agagcaatct caagcaaagt tcctgtagac aaagtaacac 780 caagtactcttccagaagag gtactagatt ttgaaaaatt ccttcagcaa acaggagggc 840 gacaaggtgcctgggatgtg atcaccagaa ctttgtaaag gtgagaaaca aacataaagg 900 gaagccaacatttatggaag aagttctaga acaccttcct ggaaaaacac aagatgaagt 960 tcaacagcatgaaaaatggt atcaaaagtt tctggctcta gaagaaagaa aaaaagagtc 1020 aattcagatttggaaaacta aaaagcagca aaaaagggag gaaattttca agttaaagga 1080 aaaggcagacaacacacctg tgctttttca taataaacaa gaggataatc aaaagcaaaa 1140 agaggaacaaagaaagaaac agaaattggc agttgaagct tggaagaaac agaaaagtat 1200 agaaatgtcaatgaaatgtg cttcccagtt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1260 tcagaaagaacgccagcgcc agtttaagtt aaaattacta ctagaaagtt atacccagca 1320 gaagaaagaacaggaagaat ttttgaggct tgaaaaggag ataagggaaa aggcagaaaa 1380 ggcagaaaaaaggaaaaatg ctgctgatga aatttccaga tttcaagaaa gagatttaca 1440 taaacttgaactgaaaattc tagatagaca ggcaaaggaa gatgaaaagt cacaaaaaca 1500 aagaagactggcaaaattaa aagaaaaggt tgaaaacaat gttagtagag atccctctag 1560 gctttacaaacccaccaaa 1579 60 1241 DNA Homo sapiens SITE (8) n equals a,t,g, or c 60ggcacganct gttatcctac ttcctgctgg ctgcctttaa acatggagct gctacacana 60caggtcctgg ctctgcanac acananggtc ctgctggaga agangcggaa ggcttcagcc 120tgggaacnga acctgggcta ccccctggct atgctgtgct tgctggtgct gacsggcctg 180tytgtgctca ttgtgggcat ccacatcctg gagctgctca tcgatgaggc tgccatgccc 240cgaggcatgc agggtacctc cttaggccag gtctccttct ccaagctggg ctcctttgcc 300tcttcagcct ccctttctgc aagatagggg caagggcggc tagatggatg tgtctgctgg 360gcaagtcata taacatttct gatcctcagt ttcatcctac aaaatgggcg taacaatgtc 420tacctactcc attgtgtgga ccaaaggaga tggttaatgt gaaagccctt tgtgaacctg 480aagtgagcaa ctgctggatg aatgtcatta cgggcacagg ctctgtgtca tctcctctcc 540tagtgcttcc acagccagga ccagagacct ccctgatgac tggggaacct ggtgatggtg 600gcctttctct ttatggggag cctgagtatg ctcagatcgc agctttcctt ccctagacat 660tgtgtaattg ggggtggggg cacacttgcc ccacwkccta gctccagcct ttcctcctct 720taggatggct caggatgagt cccccctcaa caaggcagct acccaagagt aattcccctg 780gggactttct gtgtgaatct ccccttcccc ctcctctctt ttccctttcc tggacccagc 840cactgatgta accaacctca cagactagtt gtttattata ttaatagttt gagcatataa 900agaggaactt gtgatgggag agatctaggg aggagtaaag aagtatagga atgtctggcc 960tgtattctct tcacctggga ccactgattt ttaagctgcc acattggctg gagaacaggc 1020tatggagttc ataatgtgtg gtctcctgga gctcctgttc agctctgcct tctttgaggg 1080ggcagggatg gggcagggag cacatygtaa tactaacggc ctcagagmtg ccccctgatg 1140tcctcctgcc tgttaccccg tgcctctgtc tcttaacagt gggatgatga agatgccacc 1200gtcaacaagr ktgcgctcga gctgtgcamc tttaacctgg g 1241 61 930 DNA Homosapiens 61 gaattcggca cgagctaagt cctgatatcc catgatgttt tttgttttactttgtttttg 60 gctatttcct ttttctaaaa atagccctct ctggggaatg ctgagatcttcattctttat 120 tagtatcaat ttataattat ctacatctgt aagcagttat tcgaaagtctccagatctta 180 ttctatcctg gcacccatgg tgactaaaaa aatcaaagac gttaaatctttgaaagcagc 240 cttcaaacca catactccaa ccaacttacc ttatatgtcg gggagttatggagcaaatac 300 attaattaac ttgacagaag ttgcacactt tctgtacttc tgaaccaaaatttggatgca 360 tgtttttctt tatcatgagt cacacctgat taggatttcc ttagcttttgttggggtcag 420 acaggattgt gaccaaaggc aagatttctc tgtcatctct tttgacagaatttccacaat 480 catggatttt gtaatagtcc tggacattca tcagaaagta acctgtagtggggctgccta 540 cataggattc ttcctttgaa aagccttaaa catttttcta atggttggtctctcttaact 600 aacaataaaa aacagcaaca atgcasctgg gcacagtggc ttttgcctgtaatcccagca 660 ctttgggagg cccaggcagg tggatcaact gaggtcagga gtttaagaccagcctggcca 720 acatgtgaaa ccctgtctct acgaaaaata caaaaattag ccggatgttgtgttgcacac 780 ccgtagtccc acctactggg gaggctgagg caggagaatt gcttaaacccaggaggcaga 840 gcttgcattg agctgaaatc gtaccacagc actccagcct gggcaacagagtgagactcc 900 atatccaaaa aaaaaaaaaa aaaaactcga 930 62 998 DNA Homosapiens 62 ggcacgaggc ttaagtcaag ccacctgatc agtcttgtaa ccactggagagatgagcagt 60 gtttagtcat gtccctaata ctgttattgt cagtcaccct tttacatctgtctttttctg 120 ttggcttctt tctttttagg ttgtagggga gacccattgt ctagagagaatatacgcttt 180 gacttgatga aatcccagtt taatctagaa aggtccattt tgaggttaagaacatttcgg 240 agatgtggag gtgaagatat aaagtaggtc tcagctttgg ctggccaatatgggatccta 300 cttatctcct caggggactg gacaattcgt gtcaagactc tgtgcttcaggagcctctgc 360 ttcttcctcc ttcatggtcc aactttcctg ccccttcttc atctcattagcttaaccctc 420 agttgcctga cccaagtcaa ggtgtgtgac ctggtcctga tcaccacctctttttggggg 480 cttctgcaac tgtgctctgt cctggcaacc tgcttctgta atctgtttatccccaaattt 540 gaatgagtaa taggaattgc ctaaattttg gataaattat cctacaaaataaaagcattc 600 tcacattgcc ctctcaaatc acatgatctt tgtagaaaat ggccggtccctatgaagcta 660 attgatcttt ggcatcaata gggaaattca gctgggcgca gtggctcacacctgtaatcc 720 cagcactttg ggaggccgag gtgggagggt catttgaggt caagcattcaagaccagcct 780 ggccaacgtg gtgaaacccc gcctctacta aaaatacaaa aaaattagctgggcgtggtg 840 gtgtgtgcct gtaatcccag ctactcagga ggctgaggca ggagaattgcttgaaccagg 900 gagatggagc ttgcagtgag ccgggattgc gccactgcac tacagccaggatgacagagt 960 gaggctccat ctcaaaaaaa aaaaaaaaaa aaaaaaaa 998 63 1193 DNAHomo sapiens SITE (1080) n equals a,t,g, or c 63 ggtcgaccca cgcgtccgcaccgaagccca gagggtctgg gggcacaaga ctgacgccag 60 ggtatgaaga gtgttattttcattcaaagt gttattttgt ttttccttcc aatgtctgga 120 gaccaccagg gcatctctgggctggatgag ctcccacaag cctgagggaa aggccagcac 180 tcgctagcag tggcaggcagaggcccaggc tgccgtcccc tagagtccca ggttggctct 240 gccagtgcct gtcctttaccaaagatgaat gaagcaaatg tcatgctgcc ttattcaggg 300 aaggaggagc ctgtcctgcctgtggccatg accctgcctc tcccaggcag gggcccgcga 360 tgtggaactg ctgccactgaggggggatcc agttttgtca atgcagttgt ctctgtttta 420 caagttggag tcactcttatgctgtaccca gtttctaaac tggagactgt gtgtgccctc 480 tggctctgag tacccctgctttgggcttgg gcctaggctg cattgaaaag agctgaaggt 540 tgtggccttt gcgctcctggcccagccttt gttccccact ggagcagaag gggagatgga 600 cgacacggts ggggcatctggcctggccag tgccctgatc ccagagagcc cgaggaggtg 660 tctcaggctg cctgagtcgtgacctgctag gccagagccc actccatctg gtagaaggga 720 aagcccatat gctaccaccagctgtgtcca aaaccgccag ctctgttctt cctcagccag 780 cctcgcccat ccccttgaggtctcagcccc tttcccttgt agctcctccc ctggaggggg 840 aatggcagca ggggttggggaaacagcatc tccaagcagc ttagagttgg ccatatttac 900 ctcagcctgg gcgctggtcctttcttccgg cccctcccct ccaaaatgtg cctattgcta 960 gagctcctcc ctctcaacacccagtttcct tgggagttgt cattaaagga aaaaaaaaaa 1020 aaaaaaaaag ccagtgcccagggatgggca tctccaggga gctggggatt agtgccaggn 1080 agccctgcca gccatgcctacatccccatg ggcacagaac aagccaaagc cttcgttgta 1140 tgttgacgat gcacttttatgaaatgtagt ttctatcgct gttttnagcc ttt 1193 64 830 DNA Homo sapiens 64ggtcgaccca cgcgtccgct gaaaggaaaa gcactgtttg gagaatgatc cacctttcaa 60gattttactt attgttgata atgctcccac atgtcctctt ttttacgggt gatcttcatt 120cctaatatca aagtgatatt tcttcctcca ggcaccacct ctttgatcca cacaatggat 180caaggagtta tagcagcttt taagttctac tacctgagaa gggaggactt ttgcccagtc 240ccatactgca gtggaggaag acactgagaa gactctgatg aaattctgaa cagcatcaag 300aaccttgttt aggcttggat tatgtcgcta aggactgtag gaatggcacc tggaagaaga 360cacgcaagag gtttgtcaat aayttcaaag gatttgccaa ggatgasgaa gttgcaaaaa 420tcaagaargc tgtggttgag atggcaaaca actttaacct gggtgtggat gtggatgaca 480ttgagtaatt cctagagggg gttcctgagg aattgactaa tgggttgctg ttggaactgg 540aataggagtg catagctgaa gaagaggtaa agaaaaagaa agtgcaggag aagggaaaaa 600agaactccca agaatactca cagtgatggg tttagcagaa gcttcttcag actccaacaa 660gctccttaag aagtctgaaa acatggaccc caaaactgaa aggttttcac taatagagag 720gaaagttcat ggtgcattat ctgcctacaa gcaaaaccag gattcaaaaa accctttgag 780ctggagcttc aaagcacaaa aaaaaaaaaa aaaaaaaaaa aagggcggcc 830 65 867 DNAHomo sapiens SITE (457) n equals a,t,g, or c 65 ggccgccctt tttttttttttttttttttt ttttttattg gttaaagtgc tgatgccaga 60 tgacccttga gatcccttattagtgaaatg ttctgataat aaagaagagt ttggctcacc 120 tgctggtctc caccacacaggtttataacc aagagcccta cagctcttgt cccaccctga 180 gggcctgact gacctgtggagggccccacc tttcgcctcc attcactcac ccctgttccc 240 aagaaccact gacttctttacatgaagcct actttgagta agtttttagg tacagatgct 300 gaattaccca agctgtatccaccctcactc caggcacccc gaggagagac tcaactgctt 360 ggcccagggt tagagaggcccacacgggaa ggcagagtgg agcagatgtt atttaaccaa 420 aagtctgtat cctggggctcccagctacca cagtcangaa acacattttt aaaaaatcma 480 gacccttgaa ctagcagcagtagtcaccca taccgtatac gataaataaa agtaagccaa 540 tgtttattct tctttgcataaaatcaccta taccaacact tatacattac agcatcattc 600 agttaattca agtctgaatcccagaaactc tcctgaaatc aagccacagt tcagccctat 660 tcttcctagt ttttcctgacatacttttgc ttactctata aatccacgga tattcttctt 720 gcctactccc accaaagcccaaatacacgt gaaaaaagtt aatcatgaag tttttcttat 780 tcccttacat ttagaaaatcagcatctact ctcatagact acttgtaaga agacaaattt 840 ctgctactcc ggacgcgtgggtcgacc 867 66 685 DNA Homo sapiens SITE (7) n equals a,t,g, or c 66gggcccnttt gggggccccc cctttttttt tttttttttt tttttttttt tttttttttt 60tttttttttt tttggacagg aagtagaatt tattggtgag tattaagagg ggggcagcac 120attggaagcc ctcatgagtg cagggcccgc cacttgtcca gagggccacg actggggatg 180tacttgaccc cacagccatc tgggatgagc cgcttttcag ccaccatgtc ttcaaattca 240tcagcattga acttggtgaa gccccacttc tttgagatgt ggatcttctg gcggccagga 300aacttgaact tggccctgcg cagggcctca atcacatgct ccttgttctg cagcttggtg 360cggatggaca tgataacttg gccaatgtga accctggcca cagtgccctg gggctttcca 420aaggcacctc gcatgcctgt ttggagcctg tcagccccag cacaggacaa catcttgttg 480atgcggatga cgtggaaggg gtggagccgc acccggatat ggaagccatc tttgccacaa 540ctttttacca tgtacttatt ggcacaaatt cgggcagcct ccagggcttc agaggacagc 600tgctcatatt catctgacac catgtggcca caaagcggaa actcatccac ttttgccttt 660ttccgcccca ggtyaaaaat gcgaa 685 67 801 DNA Homo sapiens 67 gaattcggcacgagtggaga tgcactgacc ttccttgcaa gagcctttcc ctgaagttgg 60 gctcctgagagaagttctga acatggctat ccctgccttt tcatcttgtc agcagatttc 120 ttcagcagctgctctacaaa tatgcaatgg accctttaag catttctcct ttacagtgag 180 cacaatgctaagctttgtca gcagatgcca ctggagcagc attgcagaag aaagcgagtt 240 tctcttcctgattttggtgt gctacttttc ttcttcttgc tccagctgca ttatccatca 300 gtggtactatgtataagacc atcccgctgt gccctgccct accacctgcc cagaggcaca 360 tccctcactgactatttggc ctgattctga gcctgtggcc accttctcac agccctgcaa 420 cacaggcactgtgtgctcca ggcctcacgt ccccagcagt ggcctgactg tgcacttagc 480 cacagcctcagtttgcctgt gctccaagaa attgcatcct atttgcccag cagctatgga 540 ccagctctctggtcctggaa aacagcaggc ttctctgaca tctagtggac tgcaaacaca 600 ccttctccaacaaggcctga ccccagcctt aaggagagaa ccgtctttcc gagttgtctt 660 tccttgggtactctccctca atcctcggat acccttgaaa gttctcttta cattgttata 720 gttattcttctatcactgtc gaataatttt ttatattaaa cttctcttgc tttacattaa 780 aaaaaaaaaaaaaaaactcg a 801 68 908 DNA Homo sapiens 68 gaattcggca cgagattttattaaaaataa gtgcttttct ctgcttacct tttactatga 60 tctaactatg atactttcaatatgctgcag actctcattc ttatctttct tttgttgtta 120 ccttgttacc tagaactcttatgtttcagc ctaatttctt catctgcaaa gacctaatag 180 gaagaaattt ttactttggtttagtgtgta taaaatctgg gaacagctaa atttcagttt 240 taatataaaa ttttgacttttatatattac ccaatattgt taaaaggaga attctatgta 300 tacctatctc ttaaaaatattgctctatat attacccgct taaaacaaca acagcaacaa 360 caaaaactta gaaggtaaacaaaaagtaat ctcataaaac atagaagggg aatacacctt 420 ggtttcagat atgcacagaaagtatgtaag ctgtacccca gaagcatcct tataaatttt 480 gcagtcagtt tctctgacctttctttacac aggagggatt tgttgtayca atctttaatc 540 taagtgtgat acaccaacttcctattgaat tgccttagag cagaagaaaa ggtataaaga 600 tgatgcatct tacttagaaatgaaaatata acaaaacaag tcatgttaaa caaggaaaga 660 tatggatctt taatcacgaacccaaaccaa gttggtggct gaacagagaa gaactgtggg 720 agccaggcca gttggcatgacagtatgtgt tcagctggtg tggagtaagc ccctggactg 780 agggtgttca gtgtggcttcagccagggga ttcagtggtg aagaaccctc ttgctactgt 840 actctttgtc tttattacaatactagtcaa gaaaaaattc tttctaaaaa gaaaaaaaaa 900 aaactcga 908 69 696 DNAHomo sapiens SITE (605) n equals a,t,g, or c 69 ggaaaatttt taaaaaatagattataatga tacatattgg tatcattaag acaacagatt 60 tgagcaaata caattaaggtgtcttatttt ttgcatcaag taattattgc tgtggtcttt 120 ctactccaca aaataattttttctttttgc agttgaaaat taactgcatt attaactaat 180 taataaaata aatcaagtggtataagggat tagtttaccc tcaagccgat gactccatgg 240 ctactgatat tagttagtttwggattttta aaaagcatat cagaccccca gtttcaggaa 300 ttgagtataa atattgcttcttgtcaccct gggacagtaa tgccttatag tggcactagt 360 caccttaagt agattacacatggttgaggt gaataaagct gcatgggaat ttgctttcgt 420 gatatatttc atttgcaaacttctacataa tcaagtttta tgtttaaaac catcggttct 480 atatatctag ctttaggaagttgcccttac aggtgggacc ttttgtgtta atctgttttc 540 tccccagtca tcttattggctatgttaaaa aaaaaaaaaa aaaaaagggs ggccgctcta 600 kaggntccaa gcttacgtacgcgtgcatgc gacgtcatag ctcttctnta agggncacct 660 aaattcaatt cactgggcggccgtttacaa cgtcgg 696 70 455 DNA Homo sapiens SITE (431) n equals a,t,g,or c 70 gtgctcaggg agctgaatac acggctgcgg gatgacaggg acgcctgcctgggcccacct 60 gctgctgctg ctgttgctgg gctcggcccc ccagacgcgg ctctggccaccttcccagtg 120 cccggtgacc agccccgagt gactcacgga ccatgagcta gaagctgcccttgcaggagg 180 cttgtcatgg gtcggggrtg cccactcagg atgcaggctc tccccagggggccccaggct 240 cgcctgactg aagacatgaa ggacctagcc taggagtggt cagggtcccgggagtggcca 300 gggtcccgtg tgtkccctct gccagtcttc gctctgtccc cgttcaatcaaccccatctc 360 agttcagcag aaaaccccct cgtcaaataa aacccactga ctgcaaaaaaaaaaaaaaaa 420 aaaaaaactc nngggggggc ccggtaccca atttg 455 71 413 DNAHomo sapiens SITE (343) n equals a,t,g, or c 71 gaattcggca cgagcggctttgggcggaac tggctttgtt gaccgggaga aacgagatgg 60 gggtgaagct ggagatatttcggatgataa tctacctcac tttccctgtg gctatgttct 120 gggtttccaa tcaggccgagtggtttgagg acgatgtcat acagcgcaag agggagctgt 180 ggccacctga gaagcttcaagagatagagg aattcaaaga gaggttacgg aagcggcggg 240 aggagaagct ccttcgcgacgcccagcaga actcctgagg cctccaagtg ggagtcctag 300 cccctcccct gatgaaatatacatatactc agttccttgt tanaaaaaaa aaaaaaaaaa 360 aaaaaaaaaa aaaaaaaaaaaaaanaaaaa aaaaaaaaaa aaaaaaaaan aaa 413 72 849 DNA Homo sapiens 72gaattcggca cgaggtataa tgccattctc ttcctctgtg aagtgcctgt tcggggtgtt 60gctacgtttt tgttttgttg tgttttctgt tgtagtgttt acatttttct tgtcgattcc 120taagaggact ttagggtact gagtcaccca tggtcatgtg ttgcagagaa gtgtcacaga 180gtgaaaactg tcttttcctt gatactacct ttagattcat atttgggaag accttcacta 240atcatgacta cataagtatt cacttttact ttcttaaggc ctttttgttt tcattctttt 300atagtaatgt ctaagccatc tggaattagt ttgttgatta tgcaagaaag ggatcgaagt 360gctttttctg agtcattatc cacatgccga aacatttatt gaatagccct ttccttattg 420atctgaaaac accttcttat aaaaccttgc attggttttt ggacttgctg tgctttcagg 480agtcagaaga acattctttt gattatkgta gctttacatw aataatacat ttkggccggg 540tgcggtggct cacgtatgta atcctagcat tttgggagac tgaggcaggc ggaacacctg 600aggtcagggg ttcaagacca gactggccaa catggcaaaa ccccgtctct acaaaaaaaa 660aaaaaaaaaa aattagctgg gcatggtggt gcctgcctga aatcccagct actttgggag 720gctgaggcag gagaacctct tgagcctggg aggtagaggc tgcagtgagc cgagcttgca 780ccactgcact ccaacttggg taacagagtg agactccatc tcaaaaaaaa aaaaaaaaaa 840aaaactcga 849 73 505 DNA Homo sapiens SITE (12) n equals a,t,g, or c 73gctccaccgc gntggcggcc cctctagaac tagtggatcc cccgggttgc caggaattcg 60gcacgagttc atctattgaa gggtgtttga gttttttcac tttttggctt ttgtaagtga 120tatagtttgg atctgggtcc ccattcaaat ctcatgtcaa gttgcagtcc ctagtgttgg 180aggtgggcct ggtgggaggt gatgggatgg tagggttggc ttctcatgaa tggttaacac 240catccccttt ggtactgtct ttggcatagt gagtttgttc tcctgagatc tcatttttta 300aaagcatgtg gcacctctcc tttcactgtc tcttgctcct gctcccacta tgtgaggtga 360ctcactcttt gtttgctttc taccataatt ggaagctttt tgaggcctct ctagaaacag 420aagctgctat gcttcctgta cagcctgcag aaccacgagc caattaaacc tttttctaaa 480aaaaaaaaaa aaaaactcga ngggg 505 74 719 DNA Homo sapiens 74 gaattcggcacgaggagaaa ggagggaagg cacagcgctg ggcagagatg ccagaaaacc 60 tagttctaatcttggccttg ctgctgtcag tgtgtggcct taagcaagtc atttttctct 120 cggcctcaatttactctaaa atgtgtaccc tcatagctac taagaaagtt gttgcaaaaa 180 ctagaaatgatgcttactgg tatttaatta gtctcaaaca catagtaggc ttttaacaat 240 tagtggctgtcattttcatt attattaggc gcttcaattt ttacatgttg gcaatctcaa 300 acataccattttcttttttt taaaaccctt ttttttkttt ttttttttga gacagaatct 360 ccagcctgggagacagagca agaccgtgtc tcagaaaaaa gtggggccgg gtgcagtggc 420 tcatgcctgtaatcccagca ctttgggagg ccagggcggg cggatcacaa gatcaggaga 480 tcgagaccatcctggctaat gcggtgaaaa catgtctcta ctaaaaatac aaaaaattgg 540 ctgggcttggtggtgggcgc ctgtagtccc agctactcag gaggctgagg caggagaatg 600 gcgtgagcccgggaggcgga gcttgcagtg agcagaaatt gcgccactgc actccagcct 660 gggcaacagagcgagactct gtctccaaaa aaaaaaaaaa aaaaaaaaaa aaaactcga 719 75 1274 DNAHomo sapiens SITE (1243) n equals a,t,g, or c 75 cctgccgttg gcggcctgagtccgcagcgc cctgckccac ccgccccgga cgtggggccc 60 aagcccccgt gaagatggtgtcctggatga tctccagagc cgtggtgctg gtgtttggaa 120 Ytgctttatcc tgcatattattcatacaaag ctgtgaaaac aaaaaacgtg aaggaatatg 180 ttcgatggat gatgtactggattgtttttg ctctctatac tgtgattgaa acagtagccg 240 atcaaacagt tgcttggtttcccctgtact atgagctgaa gattgctttt gtcatatggc 300 tgctttctcc ctataccaaaggagcaagtt taatatatag aaaattcctt catccacttc 360 tttcttcaaa ggaaagggagattgatgatt atattgtaca agcaaaggaa cgaggctatg 420 aaaccatggt aaactttggacggcaaggtt taaaccttgc agckactgct gctgttactg 480 cagcagtaaa gagccaaggagcaataactg aacgtttaag aagcttcagt atgcatgatt 540 taacaactat ccaaggtgatgagcctgtgg gacaaagacc ataccaacct ctaccagaag 600 cmaaaaagaa aagtarccagcccccagtga atcagcmggt tatggaattc cactgraaga 660 cggrgatgwg raaacagatkaagaagcaga ggggccatat tcagataatg agatgttaac 720 acacaaaggg cttcgaagatcgcaaagcat gaaatctgtg aaaaccacca aaggccgcaa 780 agaggtgcgg tacgggtcactaaaatacaa agtgaagaaa cgaccacaag tgtattttta 840 gtcatctaca cgtcaaatatcccaagacag attatgctaa atacatcgac ttcatcttct 900 aacatgatat attcaggatttacacattaa aatgattatt taaattgtgg cagtgatggg 960 gtttactttc atgaatttaaattgttttta tttcctgtaa caattgcttc caaatattga 1020 ctactaaagg cagttctgcaagatgtacta aatatgtata ttagaaatta tagaaaatca 1080 tgttgtccgt tttcaaattcatcaacagcc tagagtgcct gagatataag atgaaacaca 1140 aatccacagt atacttgaaaggagcctttt tacggttcag gataaatcag cctttgtgat 1200 gtactgtgtt tacctccttttgtgttgtat ctggtaatta aantagggcc cagattcagc 1260 aagtgacatn acaa 1274 76519 DNA Homo sapiens SITE (13) n equals a,t,g, or c 76 accaaaagctggnagctccc accncggttg gccgnccgct ctangaacta gtggaatccc 60 cccggggctgcaggaattcg gcacgaggtt ttgttttgtt tttttctaat cctgctttca 120 tactagccagtgtggggaaa aggtacaata tgtcaaagag atgagagagt gttatttctt 180 gggcaattttctattagtgt ttcttatttt ggccagttct tttatttatg tccttgtgac 240 ccaggtacttggggggccag ctacccttct ggccttttag cgtctttgaa ggagaccaga 300 catgagtgaatacctaggag agtgtcagca tgtttctgga aaattggcag agaccaagcc 360 ctgctgcagattcgtcaggc caggtgaaag ggccaggcag ttgcagctga tgatgtaaat 420 attttgtacagtagataaat aaatgtttaa aaaaaaaaaa aaaaaaaaaa aaaaraaaaa 480 aaarwaaaaaaaaactcgag ggggggcccg gtacccaat 519 77 389 DNA Homo sapiens 77ggtcgaccca cgcgtccggt ttgccatata atgagcattt tgtatacata aatttatagt 60ttaattaaat taggacattt gtaaaaaatt ggatacaatt ttattttcaa ataccttttt 120ttagctacac tcaaacactt attgaattga aattatgcac atgtttgatt tagtgatatg 180gtattacaaa acaccaatac cctgttaatt gtttctgcct ttcttctttc catgctgttt 240ttcaaatttt ctattgctat atttctagtc actaatctgt cttttgaaag gtctaatctg 300ttgttagggc catccagtga tttgttttta aattttaagt aatttatctc tataagttct 360agatcgcgag cggccgctct agagggatc 389 78 823 DNA Homo sapiens 78cccacgcgtc cgcccacgcg tccggtaact ttatgaatat aaatttacag tttgatacag 60gaattattag gagtaattct tttctgtttc tgtttataat gtagctacag tgttcttcat 120tttcagaagt taacatcaag ccatcaaacc tgggtatagt gcagaaaacg tggcacacac 180tgaccacaca ttaggctgtg tcaccattgt gtggtgtacc tgctggaaga attctagcat 240gctacttggg gacataattt cagtgggaaa tatgccactg accgattttt tttttttcct 300ctttgcagtg gggctaggac agttgattca acaaagtatt tttttctttt ttctcagtcc 360taatttgaac aggtcaaaga tgtgttcagg cattccaggt aacaggtgtg tatgtaaagt 420taaaaatagg ctttttagga actcactctt tagatattta catccagctt ctcatgttaa 480atatttgtcc ttaaagggtt tgagatgtac atctttcatt tcgtatttct cataggctat 540gccatgtgcg gaattcaagt taccaatgta acactggcca gcgggcccag caatctccat 600gtgtacttat tacagtctta tttaaccagg ggtcctaacc actaacattg tgactttgct 660ttgagacctt tcctctcctg ggtactgagg tgctatgaag ccaactgaca aagatgcatc 720acgtgtctta ggctgatgcc actacccgat ttgtttattt gcaatttgag ccatttaaag 780accaataaac ttcctttttt aaaaaaaaaa aaaaaaaact cga 823 79 2455 DNA Homosapiens SITE (2277) n equals a,t,g, or c 79 ggcctcgctc ccggaagtggagggtctaca cgaagcgccg ctgggtctgg gtgcccggag 60 gcagcagcgt tcgcggagttcgcccgctgg cccccgatca ccatgtcggc tttcgacacc 120 aaccccttcg cggacccagtggatgtaaac cccttccagg atccctctgt gacccagctg 180 accaacgccc cgcagsggccctggcggaat tcaacccctt ctcagagaca aatgcagcga 240 caacagttcc tgtcacccaactccctgggt cctcacagcc agcggttctc cagccatcag 300 tggaaccaac ccagccgaccccccaggccg tggtgtctgc agcccaggca ggcctgctcc 360 ggcagcagga agaactggacaggaaagctg ccgagctgga acgcaaggag cgggagctgc 420 agaacactgt agccaacttgcatgtgagac agaacaactg gccccctctg ccctcgtggt 480 gccctgtgaa gccctgcttctatcaggatt tctccacaga gatccctgcc gactaccagc 540 ggatatgcaa gatgctctactatctgtgga tgttgcattc agtgactctg tttctgaacc 600 tgcttgcctg cctggcctggttctcgggca acagctccaa gggagtggac tttggcctct 660 ccatcctgtg gtttctgatcttcactccct gtgccttcct ttgttggtac cgacccatct 720 ataaggcctt taggtccgacaactctttca gcttctttgt gttcttcttt gtattttttt 780 gtcaaatagg gatctacatcatccagttgg ttggcatccc tggcctgggg gacagcggtt 840 ggattgcagc cctgtctacactggataatc attccctggc catatcagtc atcatgatgg 900 tggtggctgg cttcttcaccctctgtgccg tgctctcagt cttcctcctg cagcgggtgc 960 actccctcta ccgacggacaggggccagct tccagcaggc ccaggaggag ttttcccagg 1020 gcatcttcag cagcagaaccttccacagag ctgcttcatc tgctgcccaa ggagccttcc 1080 aggggaatta gtcctcctctcttctctccc cctcagcctt tctctcgcct gccttctgag 1140 ctgcactttc cgtgggtgccttatgtggtg gtggttgtgc ccagcacaga cctggcaggg 1200 ttcttgccgt ggctcttcctcctccctcag cgaccagctc tccctggaac gggagggaca 1260 gggaattttt tccccctctatgtacaaaaa aaaacaaagc tctctttcct tctctggtga 1320 tggtttggta ggattcttttgtctctggaa gcagtgggac tgaagttctc ttcgtcctgt 1380 gcacacacag acacccccacacagttggga tcacaggctg acctgggccc atcccagctg 1440 gagctttctg ccagggtcctgggccttgac tcccccaccc tgcaggcctg gcctgaatct 1500 ggcttcttag acacagcccagtccttcctg cctgggctgg gaataagcct ctcacaggtt 1560 ctggtggaca gatctgttccccaggtcact ccagtggtct ccaggcttcc agagaaggct 1620 ggttgcctca agctcttctctgcctcataa acggatccag agaaggctgg ttgccttaag 1680 ctcttccctg cctcgtgttcctgagaaacg gattaatagc cctttatccc cctgcaccct 1740 cctgcagggg atggcactttgagccctctg gagccctccc cttgctgagc cttactctct 1800 tcagactttc tgaatgtacagtgccgttgg ttgggatttg gggactggaa gggaccaagg 1860 acactgaccc caagctgtcctgcctagcgt ccagcgtctt ctaggagggt ggggtctgcc 1920 tgtcctggtg tggttggtttggccctgttt gctgtgacta cccccccccc tccccgaacc 1980 gagggacggc tgcctttgtctctgcctcag atgccacctg ccccgcccat gctccccatc 2040 agcagcatcc agactttcaggaagggcagg gccagccagt ccagaaccgc atccctcagc 2100 agggactgat aagccatctctcggagggcc ccctaatacc cagtggagtc tggtttcama 2160 ccctgggggg tgtgtcactgtgatgggaca cgtaggagtc cacccttaaa accagcaccc 2220 tgtccctcga ggctgccgagtgggtgtgtg gactcggggg ccttcccaca aaaactnstc 2280 cggctctggg cccgagacagccgcaggccc cagccactga atgatactgg cagcggctgg 2340 ggttttatga actcctttctggtatttttt cccctctatg tacaaatgta tatgttacgt 2400 ctcaattttt gtgcttaagtaaaaataaaa acattttcag acaaaaaaaa aaaaa 2455 80 921 DNA Homo sapiens SITE(111) n equals a,t,g, or c 80 ttttcttaag ggaaaaatca cgctgtgttcttttaaaatc cctcaggttt tatgttttat 60 tgctaccaga gtctgcctcc ctgaggttcttgtatagact agttatttcc ntctgtaaag 120 aagctgttct attcgttctc gcctggtttggaacaaactg aacacttcca aaggaggcag 180 tccttgcagc cttgtctcct tccactcccctcctccccac agtcctgggc tggagcagcg 240 agtctgtcga tcccagggcc agagacaaggcagacaaagg ttcatttgta aagaagctcc 300 ttccagcacc tcctctcttc tccttttgcccaaactcacc cagtgagtgt gagcatttaa 360 gaagcatcct ctgccaagac caaaaggaaagaagaaaaag ggccaaaagc caaaatgaaa 420 ctgatggtac ttgttttcac cattgggctaactttgctgc taggagttca agccatgcct 480 gcaaatcgcc tctcttgcta cagaaagatactaaaagatc acaactgtca caaccttccg 540 gaaggagtag ctgacctgac acagattgatgtcaatgtcc aggatcattt ctgggatggg 600 aagggatgtg agatgatctg ttactgcaacttcagcgaat tgctctgctg cccaaaagac 660 gttttctttg gaccaaagat ctctttcgtgattccttgca acaatcaatg agaatcttca 720 tgtattctgg agaacaccat tcctgatttcccacaaactg cactacatca gtataactgc 780 atttctagtt tctatatagt gcaatagagcatagattcta taaattctta cttgtctaag 840 acaagtaaat ctgtgttaaa caagtagtaataaaagttaa ttcaatctaa tttttctctg 900 tggaaaaaaa aaaaaaaaaa t 921 81 678DNA Homo sapiens 81 gaattcggca cgctcttggg ggtagtggat gcgggttgaggggtttcagg tgccctgggc 60 tgtcactttg taaaggcttg ccaacctaga ttgagatgggtggtaaagga atcaattaca 120 caatgccaca catttgcttg cttctgctga atgccttagtagtttcatgt ttattgctgg 180 aagccattct cttacagcat ctagtgctgt gtaacgagctaccttaaaat gtaaaggctt 240 aaaacagcca tctttgatgt ctttgcaggt ctagaagtcaggaagggtaa ttattcagct 300 ccaagtggca ttggctctag ttactacctg atattccagggtggtagctg gagtggtctc 360 aagggtccaa gctgacctca cttacaagct gggtgccttggcagggacag ttaggaggct 420 gtgtgtagca gagcctcact cggtctttgt attctccaggcctcttcagt ggtttctttg 480 gcacttctta aatgatgtca gggttccagg agttaatgttccaagagaca ggaagtggat 540 gctgcccatc tctttttttt tgtttgtttg tttgtttgtttttttgagat ggagtcttac 600 tctgtcacca ctgcactcca gcctgggcaa cagagcgagactctgtctca aaaaaaaaaa 660 aaaaaaaaaa aaactcga 678 82 857 DNA Homosapiens SITE (493) n equals a,t,g, or c 82 gaattcggca cgaggggaaataatgtttgt ggaaaattgc ttagaggaaa tggagtatat 60 tactggtata ggtactctaaaatgtctttt gaattaagtc agagttagag ggttgtgtct 120 ctaaaccgca tcttactggtattatgctat cagcctgtat tgagagactt tataggtaaa 180 gtccaattta ggctgtttggtattatctat taaaattaga atgttcatgc tctgtaacct 240 gctacttcca cttctagaatttatctttgg aagcacatat ctgtccacag acctatattt 300 acacacatgt atgaagaatgtkttccttca cattcattca ttttaacaaa tgttttgatg 360 tgtagggcct aagctgatttgaatgcagct gaaatgcaca tatctggttg agtcmtggga 420 actgatttgc atgtgtctttctcttttatg gcttgaagag gagagaaatt tgtgcttagc 480 acattgaagg gcntacgagatacaaggagt ctgtccttag ctctgccctt tggactgttg 540 tctgaaggct aaagaagagagnacaaagaa agcttgcatt gggaggctga ggtgggagga 600 tcacttgagc ttaggagtttgagaccagcc tgggcaacat agggagactg cacctctata 660 agaaatttta aaaattagccgggttggcag cgtgctcttg tggtcccagc cgcttgaaaa 720 gctgaggtgg gagaatcgcgtgagcctggg aggtcgaggc tgcagtgcac cgtgattatg 780 ccactgcact ccagcttggcaacattgact gtctcaaaaa gattatatat ctctaaaaaa 840 aaaaaaaaaa aactcga 85783 1977 DNA Homo sapiens SITE (664) n equals a,t,g, or c 83 gcaaaaacccaaaaggggac agcagtagtg ggagaggcca gcatctgtac accccatcag 60 ggtccccgctgtgtgtgccc ctcaggcggc caccagccct accaggtcct cccctcccgg 120 caggtcttcgccttgatcgt gttctcctgc atctatggtg agggctacag caatgcccac 180 gagtctaagcagatgtactg cgtgttcaac cgcaacgagg atgcctgccg ctatggcagt 240 gccatcggggtgctggcctt cctggcctcg gccttcttct tggtggtcga cgcgtatttc 300 ccccagatcagcaacgccac tgaccgcaag tacctggtca ttggtgacct gctcttctca 360 ggtatctgcctgtggcacct ccatttgatc ttgggggagg cattaactct agggttccgc 420 agctgggagggtctcggcct ctctgggagg ggcagggagc agctcactcc tccagggcat 480 ttttaggaaagggttttcag ctagtgtttt tccgtgcttg aatggcacca gccctgcctg 540 gggtagctagaagctgagtg gacctgcagc acacccgagc agatgggctt tgcctctgcc 600 ccttttgtcccctaggctgt ctgctgtggc ccaccctgcc aaggcccgag tgtgggggac 660 tttngaggtggctcccggcc cggcttccaa gtcctcccct ccatagtgtg gaagcntccc 720 ccgggaggtccctgccctac ctgcccgcgt cccctcccag agtcctggaa agcccctccc 780 tttccatggaactgacgctt cacccgtcct cttctcagct ctctggacct tcctgtggtt 840 tgttggtttctgcttcctca ccaaccagtg ggcagtcacc aacccgaaga cgtgctggtg 900 ggggccgactctgtgagggc agccatcacc ttcagcttct tttccatctt ctcctggcgc 960 tacaaggctggcgtggacga cttcatccag aattacgttg accccactcc ggaccccaac 1020 actgcctacgcctcctaccc aggtgcatct gtggacaact accaacagcc acccttcacc 1080 cagaacgcggagaccaccga gggctaccag ccgccccctg tgtactgagc ggcggttagc 1140 gtgggaagggggacagagag ggccctcccc tctgccctgg actttcccat gagcctcctg 1200 gaactgccagcccctctctt tcacctgttc catcctgtgc agctgacaca cagctaagga 1260 gcctcatagcctggcggggg ctggcagagc cacaccccaa gtgcctgtgc ccagagggnt 1320 tcagtcagcygctcactcct ccagggcact tttaggaaag ggtttttagc tagtgttttt 1380 cctcgcttttaatgacctca gccccgcctg cagtggctag aagccagcag gtgcccatgt 1440 gctactgacaagtgcctcag cttccccccg gcccgggtca ggccgtggga gccgctatta 1500 tctgcgttctctgccaaaga ctcgtggggg ccatcacacc tgccctgtgc agcggagccg 1560 gaccaggctcttgtgtcctc actcaggttt gcttcccctg tgcccactgc tgtatgatct 1620 gggggccaccaccctgtgcc ggtggcctct gggctgcctc ccgtggtgtg agggcggggc 1680 tggtgctcatggcacttcct ccttgctccc acccctggca gcagggaagg ctttgcctga 1740 caacacccagctttatgtaa atattctgca gttgttactt aggaagcctg gggagggcag 1800 gggtgccccatggctcccag actctgtctg tgccgagtgt attataaaat cgtgggggag 1860 atgcccggcctgggatgctg tttggagacg gaataaatgt tttctcattc aaaaaaaaaa 1920 aaaaaaaaaaaaaaaaaaaa aaaaaaaaaa aaagggcggc cgctcgcgat ctagaac 1977 84 1149 DNAHomo sapiens SITE (837) n equals a,t,g, or c 84 acccactgac aggcattatgacctaacagg aggttggtag cagtagatcc aagcatgcat 60 gttgcctggc ctgtagattggccttatcag gtttctgggt gcctctgcct taagatcctg 120 aaggmaaatt ttgtttcaacagtttggaag tcatctgtgg gtccagcttg actttggagg 180 aataagaaga tacttctagagtatgggaat gattccagat aatttctggg atttgaatct 240 acttgagttt aagggcctgggacctaattt ggtttagtat agaatttgaa gaattaattt 300 ataggcagct gaatacccaaaacttgggtg gtggtcctgt ggtttggctg agctgtccgg 360 gcataacctg gttctctgttatgttaaggc tttctgggaa gccagccact ctgcgcagga 420 gtgaaacatg aagttgttttctgaggacct gttttggtgg gattgtttgg gcagaggact 480 gtgtttatgc agggcaaatcccagaaagat aagaggaagc tagagaaact taatgtacct 540 gaattcttca tggtgtatttgcaaactaac ttaacataga ttcttttgac tatggtaagt 600 ttgaatctct ccttgccaaacaacattata agtttagttt tcttcttcct cttgcagccg 660 gtacagaaag gtgtaagtggtggctgaaaa ttgaggaagc ttcatctgac caatgtgggt 720 gctggtttct tgtgaaatgtgtccctaagc ctccttctcc ttgcaggcag ccacccaccc 780 aggtgtctaa gataggacatgctcctttct ttctctaatc csatcctgag gttgccngca 840 aagccaatat gaccactactgagaaatagt aatgacttct acaaatgcaa gggtcttacc 900 ctcctctttc ccttaaamaccctccctttt ccttagaccc cgtttttgcc atcccccaaa 960 tgtgtggtat ggtgaaactaatcccctgaa tgtgaattgc tatccttatt gccctattaa 1020 agaagagcca gctggtatattgtcaggaag cactatttaa aatgtgaact gttatagagt 1080 aaataaataa atactctacaggaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1140 agggcggcc 1149 85 767DNA Homo sapiens 85 catgaaaaca cattctctta tagtttttaa attcatcatccaagagttcc tgctctttga 60 tgatgagaca tacctggtag actccaaaac agagagcagacgcctagtat ctttgttctg 120 gggtgtgcat taagagtaca ttgacctgtc tgtctccagtcttgactctt ttggaagaga 180 gatgctagta ctgatgacaa cctgcattct ggctgcggtgtgygtccaca ctgcacagtg 240 tgcaccagac tctcgtatgg acaatgactg tccctcacatcaggcgcaga tccattttag 300 agcctcagaa gtcaggagag ggtggacttt caaccacgactgaaaacact gtctttctta 360 ggacatgctg tgtgtatgac acacttacag atgtctgtgctcactgatgc ttgttgatgt 420 gtcatcgcac atcagtgaca aacatttgtc atgtttttgcctttggtgga acttctttat 480 tatactcact ttcctcccaa accatttttc tcaacttcatcatgaagcaa atgtcatgtg 540 gtcattctgt gatggggctc agggctaggt taggtgatgatttctgaaag ctcagagacg 600 tgaaggaaaa aggacatcag tgcttggatc ttagctcttataagcctcac gtgcaacaat 660 aaacccgagt tcaagaatca gattcttaga tagattggtttggtagcaaa tgacaaaaaa 720 ccaacgtaaa tatgcttcgg caaaaaaaaa aaaaaaaaagggcggcc 767 86 728 DNA Homo sapiens 86 aaatgattta gtgacctata caagtagcctgcagtaccgg atccgaattc ccggtcgacc 60 cacgcgtccg gtgaaaacag cagagtgctactccatacca ctgggatctt gtccagtaaa 120 catccagaga gtgaggttag gaaataaaaagtatataaat attagatgcc tagaaatgca 180 agtcacttta aagattttat gtgaaatagaaaaaaaagag aggagaggga ctcattgtct 240 tgtaatgggt ccttcccaga gagaggtgactgtccagtgg caccgggccc ttttcctcct 300 tcccctttta ctcttatcaa ctaggacagaaactaagaat tttggcttca agtggctaaa 360 agactgatgg gggaaaaaag aaaatagaaaaaaataacag agagactgac gctctaggca 420 gttacaagtc caagaaaaaa gacagaaacttttaagtatt gagccaaaac caggtctagc 480 aamcataatg ctggccctag attatttattaatttatgaa gaaacttcta gatatggggg 540 tgacaaaagg aaattaaatc cattatatatgcatatattt taatgtaaat atataataga 600 taaattatgt atacataata tataaccaaattgaaacagt tttacaattt ggtttgactg 660 gaaattcaaa atccatatat taatttttgtagtaaaagtt tatgtaaaaa aaaaaaaaaa 720 gggcggcc 728 87 735 DNA Homosapiens SITE (376) n equals a,t,g, or c 87 gaattcggca cgagtagcagcttgattttc tgttagccta tgaaatgtta ttgtcctata 60 aaaataactt taaactgatttaatatttca tatttacatt atatgaaaat caattacatt 120 ataaaaggaa tccctaatgcagaaacaaag atgcaacttt caaaattctt attattccta 180 tttgtatata cacgagagaacccaaccagt gcctgtgttt ggggggaaaa gtcaacagtg 240 tagttctaaa ccttatcccaaacagaaaat gtggktaatg atgtcacttt ccttgctggk 300 catcattagg cttaaattaaatgctgaagc tgtcatcaaa gagtttacac taaaatcttc 360 agggctttaa ataaanggttaagtccagct tccaaacaca attttccaca ttagcagctc 420 caatcttctt aaataaagctctgttttcct atatttttat gactgctgag accccacagg 480 gaccaatatt tgtattcaaattacatttca tggtttccca ttgtttcaca atgagttcta 540 ataaatggga tttactataataatccaagt atgacatagc cggtatgctt tcatgaatgt 600 ttttatgtag attttcctcccatgaacatg agtaaataaa tctgtttcct gaatggattg 660 tggttgcatt taaagctctgtaataattct aataaattta ctctatagaa aaaaaaaaaa 720 aaaaaaaaaa ctcga 735 88889 DNA Homo sapiens SITE (117) n equals a,t,g, or c 88 tgttaggttaattattgctt cacatgtggt cacggtttga aaacttattt tggggggagt 60 ataaagtagaatacagagat tccttgctca tagctcctac tgctatcggg gaacaancct 120 tgagggtgagaacgtggatt gattcttgat tgatagtggg gattccatta tctgtatttg 180 gcagttatggcctgctgcgg tgtatagaag cttctttcca ttcattttcc cgaattttca 240 tactgctcaaggaacagttg ggggggaatg ggcagaaggt tgggcacttg angtatttga 300 gctatcggtaataactgact ttttagggcg cacagatttg nagtagagcc atggtagtag 360 ttagtaccaatgggtttttg ctgcttctac tctttcttaa cagaaaaagt ggattgtgtt 420 catataggaaagcagttcac agactgtctt cctgcccctc ccgccaccaa gctggaccta 480 gaatcaagtgtgactttaaa tggggaaagc tgtgttacag ttgtgcttaa gccactgctg 540 tggcttaacctcacctatgc ataagaattt gctcgtggct ggccgggcgc ggtggctcga 600 gcctgtaatcccagcacttt gggaggctga ggcgggcgga tcacgaggtc aggagattgg 660 gaccatcgtggctaacacgg tgaagccccg tctctactaa aaatacaaaa aaaattagcc 720 gggcgtggtggcgggcgccg ctagtcccac tactgagtcc caggctgaag caggagaatg 780 gtgtgaacccaggaggcgga sttgcarcga gccgagatcc tgtcactgca ctccagcctg 840 ggcgaagcgagactctgtct caaaaaaaaa aaaaaaaaaa aaaactcga 889 89 569 DNA Homo sapiensSITE (1) n equals a,t,g, or c 89 ntaaggtgtt gattctggat cacgggataccattcctgtc macaccccga ccaggggcta 60 gaaaatttgt ttgagatttt tatatcatcttgtcaaattg cttcagttgt aaatgtgaaa 120 aatgggctgg ggaaaggagg tggtgtccctaattgtttta cttgttaact tgttcttgtg 180 cccctgggca cttggccttt gtctgctctcagtgtcttcc ctttgacatg ggaaaggagt 240 tgtggccaaa atccccatct tcttgcacctcaacgtctgt ggctcagggc tggggtggca 300 gagggaggcc ttcaccttat atctgtgttgttatccaggg ctccagactt cctcctctgc 360 ctgccccact gcaccctctc ccccttatctatctccttct cggctcccca gcccagtctt 420 ggcttcttgt cccctcctgg ggtcatccctccactctgac tctgactatg gcagcagaac 480 accaggcctg gcccagtgga tttcatggtgatcattaaaa aagaaaaatc gcaaccaaaa 540 aaaaaaaaaa aaaaaaaaaa aaaactcga 56990 334 DNA Homo sapiens SITE (321) n equals a,t,g, or c 90 agaaaatgaacaaactagtg agaaacattg taaacatata gtgtagatga taactctgaa 60 cttaagtacaagataatgat gaatattctg ctgcttaagt atatcttaga aatattaatt 120 cttagtgaaaatcttaacct attcaacatc acttatggta agtataactt atttttccta 180 tacaggtattaaatatataa tttatatgcc agtcacattt cctcacacta aataaggcag 240 cagacacatatatttaatat catgggtatg cattttaggt tctaaaacct aaggtatgtg 300 gatttcttaaagccatatct naaatatttt cacc 334 91 795 DNA Homo sapiens SITE (3) n equalsa,t,g, or c 91 cgnaccattt tttttttttt gaatatcatc agcttacttg actggcaagggcagaagctg 60 gggttggcct gaactctgcc aaacaaatat caaagtgtat ttaatagttaaatttgtgcc 120 ctttcccttc ttgctgcacc catgttgtca cttaaccccc aggagttatttattatcttt 180 ttgttaaagt caggctcatt tggggtaatg tgatgactgt ttaggtttacatgaccctcc 240 tctcctttcc ctacccccaa atatgtatat atacatatat aaaatatgtatatattttac 300 ctatataaaa tatatatata tacacatata tgtatctata ttcctttgtttctttgcctg 360 cttatactgg ccataaaaga gggagctgcc ttcaatgtat aaagtataagaagagtgcca 420 gggaatgcca taatggaggc ttttggatct gaatttggac catttcactaaagagaacat 480 gagtttgctc agccctttcc tcacaagagg gagggccccg gttccccagacttctccacg 540 cgctggctcc ataaaggcca gctttggccr ggctgccaca ggggcctgaggagctcactc 600 tgggcctacc tggtttcagt tagagggtcc tcctgttatt tttccatttaaaaagtatgt 660 cctcagaaaa ctgtactgga aggatgggtg gcaggaactt gtatagttcagcttccaaca 720 ctttggaaca gattaaaaag ggaatctttt aaataaaaac gtataaaaataaaaaaaaaa 780 aaaaaaaggg cggcc 795 92 577 DNA Homo sapiens 92tagtggatcc cccgggctgc aggaattcgg cacgaggctg cacgaggttg ttgagaggat 60caagtaagat aatgaatgaa agtgtctatg acgacagtac tagttcttac acaccatccc 120tccacatttt gggatgtctg ttgctgctct tccttggggt ggaaagagca ctggagccct 180tctctggtct ttgtgcttct ttacatgatg tgagacctat agtaaacccc ttaacctcct 240tcagcctcat ttattagaga gagagagaaa aaaaaaggtg attttaaaaa aatctgtttt 300cggccaggtg cagtggctca tgcctgtaat cccagcactt tgggaggccg aggcaggtgg 360atcacctgag gtcaggagtt cgagaccagt ctggctaaca tggtgaaacc ctgtcactac 420taaaaatacm aaaaaatcag ctactcggga ggctgaggca ggagaatcct atgaaaacgg 480gaggcagagg ttgcagtgag ccgagatcgt gccattgcac tctagcctgg gcaatgagca 540aaactttgtc tcaaaaaaaa aaaaaaaaaa actcgta 577 93 968 DNA Homo sapiensSITE (904) n equals a,t,g, or c 93 gaattcggca cgagcttact ttcactcaccgcctgtcctt cctgacacct caccatgtgt 60 acgggaaaat gtgcccgctg tgtggggctctccctcatta ccctctgcct cgtctgcatt 120 gtggccaacg ccctcctgct ggtacctaatggggagacct cctggaccaa caccaaccat 180 ctcagcttgc aagtctggct catgggcggcttcattggcg ggggcctaat ggtactgtgt 240 ccagggattg cagccgttcg ggcagggggcaagggctgct gtggtgctgg gtgctgtgga 300 aaccgctgca ggatgctgcg ctcggtcttctcctcggcgt tcggggtgct tggtgccatc 360 tactgcctct cggtgtctgg agctgggctccgaaatggac ccagatgctt aatgaacggc 420 gagtggggct accacttcga agacaccgcgggagcttact tgctcaaccg cactctatgg 480 gatcggtgcg aggcgccccc tcgcgtggtcccctggaatg tgacgctctt ctcgctgctg 540 gtggccgcct cctgcctgga gatagtactgtgtgggatcc agctggtgaa cgcgaccatt 600 ggtgtcttct gcggcgattg caggaaaaaacaggacacac ctcactgagg ctccactgac 660 cgccgggtta cacctgctcc ttcctggacgctcactccct tgctcgctag aataaactgc 720 tttgcgctct caaaaaaaaa aaaaaaaaactcgagggggg gcccggtacc caattcgccc 780 tatagtgagt cgtattacaa ttcactggccgtcgttttac aacgtcgtga ctgggaaaac 840 cctggcgtta cccaacttaa tcgccttgcagcacatcccc ctttcgccag ctggcgtaat 900 aacnaanaag cccgcaccga tcgcccttcccaacagttgc gcagcctgaa tggcgaatgg 960 caaattgt 968 94 553 DNA Homosapiens 94 gaattcggca cgagtcccta aacagttaaa atgtcacagc tgtttcttataatgcttaca 60 ttcatatttc taaataacat gtttataatg catctaactt ccttccatggaaaaagagta 120 tttggctttt taaaccaatc gagtcacatg catgctttcc cccttccacgttggactaca 180 tcaatattta gtgttagtat ttttataaat agataaatat tgttcgcaaattttatttgc 240 tgtctattgc tgtgtaacaa attcctccaa aattattggc tttaaacaacatttattatc 300 ccatagtttc tatgagttga gaatctaagc aggcttagct gggtccactagctcggggtc 360 tctcacaagg ccacagatca aggtgttggt cagtggtttg tgcccttagtcccagctact 420 tgggaggctg aggcaggagg atcacttgaa cccagtagtt caaggctgcagtgagcwakg 480 gttacaccac tgcactccar cctgggtgac agagcaagat gccatctcttaaaaaaaaaa 540 aaaaaaaact cga 553 95 968 DNA Homo sapiens 95 ggcacagcaaccgtcactgc ctatcagaat cagcagatta ctcgcctgaa gatagatagg 60 aatccatttgctaaaggctt ccgagactcc gggcgcaaca gaatgggttt ggaagccttg 120 gtggaatcatatgcattctg gcgaccatca ctacggactc tgacctttga agatatccct 180 ggaattcccaagcaaggcaa tgcaagttcc tccaccttgc tccaagtact gggaatggcg 240 ttcctgccactcaccctcac cttttgtctg gctcctcttg ctcctctcct gccttccatc 300 tggggcccaacaccagccag ctgtgtagtc tggcccctgc tgactattct gcctgtgccc 360 gctcaggcctcaccctcaac cgatacagca catctttggc agagacctac aacaggctca 420 ccaaccaggctggtgagacc tttgccccgc ccaggactcc ctcctatgtg ggcgtgagca 480 gcagcacctccgtgaacatg tccatgggtg gcactgatgg ggacaccttc agctgcccam 540 agaccagcttatccatgcag atttcgggaa tgtcccccca gctccagtat atcatgccat 600 caccctccagcaatgccttc gccactaacc agacccatca gggttcctat aatactttta 660 gattacacagcccctgtgca ctatatggat ataacttctc cacatcyccc aaactggctg 720 ccagtcctgagaaaattgtt tcttcccaag gaagtttctt ggggtcctca ccgagtggga 780 ccatgacggatcggcagatg ttgccccctg tggaaggagt gcacctgctt agcatggggg 840 tcagcagagtttctttgact ctaggaccct aggaagctta actctgtcat catctcaagt 900 atctgcacatatggtctgat gaagccttta aagttaaatg aacatttggg atctgtctaa 960 acatattt 96896 697 DNA Homo sapiens SITE (19) n equals a,t,g, or c 96 aagaaaattaccctcactna aaaaaaacaa aaactaaaag ctcgcacgcn tgcaggnacg 60 acactagtggatccaaagaa ttcggcacga ggccacatcc caccggccct tacactgtgg 120 tgtccagcagcatccggctt catgggggga cttgaaccct gcagcaggct cctgctcctg 180 cctctcctgctggctgtagg tctccgtcct gtccaggccc aggcccagag cgattgcagt 240 tgctctacggtgagcccggg cgtgctggca gggatcgtga tgggagacct ggtgctgaca 300 gtgctcattgccctggccgt gtacttcctg ggccggctgg tccctcgggg gcgaggggct 360 gcggaggcgacccggaaaca gcgtatcact gagaccgagt cgccttatca ggagctccag 420 ggtcagaggtcggatgtcta cagcgacctc aacacacaga ggccgtatta caaatgagcc 480 cgaatcatgacagtcagcaa catgatacct ggatccagcc attcctgaag cccaccctgc 540 acctcattccaactcctacc gcgatacaga cccacagagt gccatccctg agagaccaga 600 ccgctccccaatactctcct aaaataaaca tgaagcacaa aaaaaaaaaa aaaaaaaact 660 cngggggggggcccggttan ccaatttggn cctaaag 697 97 866 DNA Homo sapiens 97 ttttagttcattattctctt ctattaagag aaattcactg ttaaaaaatt gtttcccatt 60 tccgtatctgaaataatgac tgtagttgag gtgatcttgc cctgggtctg aaatcatact 120 tccaaaccaaaaaggacttt gaatacaaaa cttttaagaa atcttgtatg aatacaagct 180 atatctgaaaaattgtgttt tataatattg atgcctagtt ttgccccagg ccatctgcag 240 tgtggttactatgcaaagaa tgctggtgtt gctgtttttt tttttttctt tgttggctat 300 taacccagcggagacaatat gtggctatgg tagtacttgg aagttctagc attacacaga 360 ctagcttccatttctctcat agaggtcatt ttggcattta aaacacatac ttttagaaaa 420 cagatttggatgtatgtaaa cacagggtta atccaccaca ctctggatgc tagagctgtt 480 gacaaagtcatgctttgcag attttaaaat aaactttttg ttactcttac agcttggtat 540 tttcccctcctatttttttt acctcctcta aataaacctc tttgttaaat aattgatgtt 600 tctggatcatagaaaatagt aagtttaaaa tacagaatat ttccaagcta actacaaatc 660 tgatgacagttttttgagtg tgcacttttc cttttatttc ttaggtcctt tttggtcctt 720 tgcaaacatagtaagattcc atatttgtgt cccaactgtg gtaatattgc tgacttctta 780 ctggaaaacagtcagctcta ggtagcattt cttctgtgtg gtatttaagt taaattatta 840 ccaaaaaaaaaaaaaaaagg gcggcc 866 98 1368 DNA Homo sapiens SITE (637) n equalsa,t,g, or c 98 ttcctgtgtg ccctgagccc gctggggcag ctgctgcagg accgctacggctggcggggc 60 ggcttcctca tcctgggcgg cctgctgctc aactgctgcg tgtgtgccgcactcatgagg 120 cccctggtgg tcacggccca gccgggcycg gggccgccgc gaccctcccggcgcctgcwa 180 gacctgagcg tcttccggga ccgcggcttt gtgctttacg ccgtggccgcctcggtcatg 240 gtgctggggc tcttcgtccc gcccgtgttc gtggtgagct acgccaaggacctgggcgtg 300 cccgacacca aggccgcctt cctgctcacc atcctgggct tcattgacatcttcgcgcgg 360 ccggccgcgg gcttcgtggc ggggcttggg aaggtgcggc cctactccgtctacctcttc 420 agcttctcca tgttcttcaa cggcctcgcg gacctggcgg gctctacggcgggcgactac 480 ggcggcctcg tggtcttctg catcttcttt ggcatctcct acggcatggtgggggccctg 540 cagttcgagg tgctcatggc catcgtgggc acccacaagt tctccagtgccattggcctg 600 gtgctgctga tggaggcggt ggccgtgctc gtcgggnccc cttcgggaggcaaactcctg 660 gatgcgaccc acgtctacat gtacgtgttc atcctggcgg gggccgaggtgctcacctcc 720 tccctgattt tgctgctggg caacttcttc tgcattagga agaagcccaaagagccacag 780 cctgaggtgg cggccgcgga ggaggagaag ctccacaagc ctcctgcagactcgggggtg 840 gacttgcggg aggtggagca tttcctgaag gctgagcctg agaaaaacggggaggtggtt 900 cacaccccgg aaacaagtgt ctgagtggct gggcggggcc ggcagcacaggggaggaggt 960 acagaagccg gcaacgcttg ctatttattt tacaaactgg actggctcaggcagggccac 1020 ggctgggctc cagctgccgg cccagcggat cgtcgcccga tcagtgttttgagggggaag 1080 gtggcggggt gggaaccgtg tcattccaga gtggatctgc ggtgaagccaagccgcaagn 1140 ttacaaggca tcctcaccag gggccccgcn tgctgctccc aggtggcctgcgcatggctt 1200 atgctcaagg acctggaaac ccatgcttcg agacaacgtg actttaatgggaagggtggg 1260 tgggccgcag acaggctggc agggcnggtg ctgcgtgggg ccctctccagcccgtcctac 1320 cctgggctca catggggcct gtgcccaccc ctcttgagtg tcttgggg1368 99 613 DNA Homo sapiens SITE (25) n equals a,t,g, or c 99gaattcggca cgagcgggac gcggntgaag atagcctgcg gagtgtccgg gcggaacacg 60gttgcagcac tcccagtaga ccaggagctc cgggaggcag ggccggcccc acgtcctctg 120cgcaccaccc tgagttggat cctctgtgcg ccacccctga gttggatcca gggctagctg 180ctgttgacct ccccactccc acgctgccct cctgcctgca gccatgacgc ccctgctcac 240cctgatcctg gtggtcctca tgggcttacc tctggcccag gccttggact gccacgtgtg 300tgcctacaac ggagacaact gcttcaaccc catgcgctgc ccggctatgg ttgcctactg 360catgaccacg cgcacctact acacccccac caggatgaag gtcagtaagt cctgcgtgcc 420ccgctgcttc gagactgtgt atgatggcta ctccaagcac gcgtccacca cctcctgctg 480ccagtacgac ctctgcaacg gcaccggcct tgccaccccg gccaccctgg ccctggcccc 540catcctcctg gccaccctct ggggtctcct ctaaagcccc cgaggcagac ccactcaaga 600acaaagctct cga 613 100 685 DNA Homo sapiens 100 gaattcggca cgagcctcagccaccccagt agctaggact atagacacaa gctagccttt 60 ttatacttac tgttttcatcaaatgtcttt ttccaactag tttccaacct gtctttgtat 120 ttgaagtgca tctattgtagatagttcagt gttgctttta aagtgcttac tccatttgtg 180 tttagtatgt tgacatggttggatttagat ctactatttt gctttctgtt tttattcctg 240 tttatccttt tttacttcttacagcttaat gaattttggg gggggaatcc attttaattc 300 tctcttgggt ttttagctacatcttcttta ggattgcact agagattaca atatacattc 360 ttaacgtctc acccttttgcctggggcggt ggctcatgcc tgtaatccca gcactttggg 420 aggctgaggt gggtggattgcctgagctca ggagttccag accggcttag gcaacatggt 480 gaaaccctgt ctctatgaaaaatacagaaa cattagctgg ttgtggtggc acacacctgt 540 agtcccagct acttgggaggctgaggtggg aggatccctt gagcctggga ggttgaggct 600 gcagtgagct gagatcataccactgcattc tagcctgggt gacagagtga gatgctgtct 660 ccaaaaaaaa aaaaaaaaaactcga 685 101 646 DNA Homo sapiens 101 tcgacccacg cgtccgataa ctttttcaagcaatatcagt gagtgggtcc catcgacagg 60 gttccaggac ctggaacact ttaacagaaggaaatgccga agcagcttgc acagttgctt 120 tacagacttc caagaggctg attctggcttcaagatggag ccttggagtt ggtttttttt 180 tttttttttt ttcttccctc aaagaacctgcggttgcgct ttgtgtgttt tgtttttgtt 240 ttccatttgg gggccccatg ggaaagagcttctgaactct ttcctttatg aactcccact 300 gtgttcctat aaaggccctt ttctttcttagtgttgtaag ttacattttc attatgcccc 360 atcacatctt ctttactgta aaaatattaaaaagctgttt ccaagtggga cagctaatga 420 agctctaatt attgcagaca tatttttgagatgtaaaaaa aaaaatttaa agttaaatga 480 taagtcttag aggcgagtga ggaataaaatggatgtaaac atttacatgg gatgcattag 540 aattctgctg tgtgtactgt cttttggttgaaacaaatta tgaacagtga ctaataataa 600 aaagtcaata cccaawraaa aaaaaaaaaaaaaaaaaagg gcggcc 646 102 826 DNA Homo sapiens SITE (726) n equalsa,t,g, or c 102 ggtcgaccca cgcgtccggc tccctttgtt ttggtggcag ccttcttgtgctgtatactt 60 gttccctagg gtgtataata atatgtgcac tagagtgcta ggtaccctaccacattgctg 120 ggaccttgcc acactgctgc agccttccag taggatatgg gggaatgtcagtgaggctcc 180 agggatgtag atatgtaggg aatgttggac cccagggcaa catgcaatctggtaggagtt 240 gggctctcaa aatggtgctg ctgtgtaaca gctgcttggg tcttggggtagggagtgtag 300 gacccagcat gagctccctc tttggagcag tgctgtctga gactccaggcagctccgtgt 360 attagtctca ggacctgcaa aggcctaggg gctctttttg ggtaggactgcaggagtctc 420 catggtggga atgtgaacca ctggaaatct ctcatttacc atttccctgtactggagatg 480 ctttctgggc tcccagatga tactarctgg gctggttgcc tcamttccttctccctctgt 540 gcataaggca ttttctgtca cttctctgct gaactctagt gttctttcttagaggctgta 600 ctcaaagttt cattatccat tcagtatttt tattcttctt tgtggaggtggcaagtgcta 660 ggtgcctcta gtcaatcatc ttgaagcccc ctgttatgtt aaagtctttaatggaaaaag 720 aagacnacat gcatgaccag gcagatactt tgagcagagt cataggaactgctaaaaaaa 780 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaagg gcggcc 826103 586 DNA Homo sapiens 103 gaattcggca cgaggtggct atcagatttg gggttctactctatgagact tttaagtcat 60 tatgcaattt ctttattttw atttttttga caagaagtctggagcatgat tacattatgc 120 attttcttac tctttaaagt atttgtgggg ataatccttcattatttgat tggcaaaaat 180 atatatgttt atagtgtgta acatggtgat tggatatatgtacacattgt ggaacagcta 240 aatcaagcta ataacaaatc agttacctca catacttattttgtggtgaa aacatgtaaa 300 atccactctc ttagcaattt tcaagcatcc aatacattgttawtaactgt agtcaccatg 360 ttatacaata gatctcttga acttattctt cctgtctaactaaaattttg tattccttga 420 tcaacatcta cccaatccct cactgttctc cagcctkgataactaccatt ctactctctg 480 cttctatgaa tttgactttt ttttttttta gattccacatatgtgagatc gcgcagtatt 540 tgtctttctg tgcctggctt atttcactta atataaagtccctcga 586 104 628 DNA Homo sapiens 104 tacagcagtt taaaaagcag tgtctttctttgagagacag gaagtctagt gaagagccag 60 tattttaggg atagataatg aaagaggctgtcatttcaga cattttaatc ctctgaaaga 120 atacaaaaga aaaaaaaaag aaaacaaatctttcagaatt gtttgaagta agaacaagac 180 aagaggaggt gattggtgtg ttactgttctacgaaaaagg agaaaaagct tcatgaaatc 240 gccattcagc aaggacagaa ctggagatggcttctctttt acaaagaaat ctctgtccca 300 ggctttcagt ctgtttggtg ttcatacaagtgtttgtgtg ttgtgtggaa ggcgggggaa 360 ggcgggtgaa ggcggtcctg ttcagggccccctttggtga acacagcagg caaaatactc 420 tcgtcatccc cagccaaact ggcctgcaagcgcactgact tccacatccc tagcatttag 480 gcctttgaat agaagctgac acgtagcagccagctgaaca agtatttaat gaggagcaac 540 acaactccaa gaagggctcc ttagtgtattgtcaagttgc tgcagccttg tgagatggaa 600 aaaaaaaaaa aaaaaaaaaa gggcggcc 628105 558 DNA Homo sapiens 105 agctctaata ttactcactw tgaaggsaaa gctggatacgcctggcaggt accggttccg 60 ggrattcccg ggccccatca caccctatgg gggagagcgaatgttacagg aggctttctg 120 gtgcctcgtg cacatggact gtgcatgtgg attttgcctaaggtcagcct tatatgcatt 180 gtggaactag ggtatggaaa accatgaaac atgattattttcttctagca tgcctgtcta 240 tgacttcaac tggtggtatt ctttgtactt tataatctacattatcatta atacctacat 300 cttcaagtct gtctttctgg ccatggtgta cagcaattataggaagcatt ttcacatact 360 gtgtgtgtgt gtgtgtgtgt tttgtagtga tgaacagaacttgttattta cccaattcta 420 ttatctatca taatagtaaa ttagctacta taatagacaaaagtatgact ctcagttaaa 480 taagagattt tttaaaaact tgttacaaaa aaaaaaaaaaaaararaaar aaaaaaaaaa 540 aaaaaaaaaa gggcggcc 558 106 756 DNA Homosapiens SITE (230) n equals a,t,g, or c 106 gaattccaat gtccacaggtgatgggagag atgctgagaa agggtggcca gtgagtgagg 60 aggaaaacca gaggagtgtgtatcctgggt accctgaatg tgatgagcga caagctgtcc 120 cccagcactg tgccattgcttctcccagtt ctcttcaaag tcaccatcct gcttcagcgt 180 gtgtgcccag aagatagcccttcctcttct gtgcttccag aatccgtagn cagggaatag 240 gaatacatgg acaagtagcatgcagtgcag tgagaatgta taacaacaga tgactctggg 300 gaccaaaatc aaatggggccagctacaaag agggcaggaa atccccacag gtgattttac 360 tgtgaggaat tttatgaggttcagcatcat atattgttag gagaaaatgc tgttttgata 420 agcagagata tgagaaaagtaaacgggaac tatgatttag agatctcatc tgrttacttt 480 gtcctattcy cagtttwattactaaagagc agtaaagcca aggagaaagt agtaaagatt 540 agatgaatgg ttagcatgtgaaacctgaaa ggaaccagag tgatttccct cgaggaacaa 600 atgcacttct cttacatatgaaagatgatg tgttctgtgt tcccatagaa tctagggaaa 660 gaaaaagtga gcagatactctgatatgagc aatataactt aggtgtaaaa aaaaaaggaa 720 ttcgatatca agcttatcgataccgtcgac ctcgna 756 107 1146 DNA Homo sapiens 107 cccgtccacaatgcagcaga ctcttcccaa ggccacctag caagcaaggt tgatcggatc 60 atctaaactggccgcctcct gaatatttca ctgaatcctg gcgttcatgt tgaagcagac 120 aaaatgagaaaggaggaggg cattgctcac ctctcaatag cttttttcgt tcaagttcta 180 tgtctttatcagctcttgcc tgtgatttta ccccaattca accttgggag tgggaagaat 240 atgaacagataacccttggc ctaacagctc catcaaacct ccttgagagc aactacctag 300 gccaggctagtgagtgcttt gtgaggaagc tggtcagaag gttccctcaa ctccttcctg 360 gtcctcctggacactgcaga aaagacttag gggatcccca gcagaggcca attgctctcc 420 ttccttccctgccccaccag gaaaggaata acgtccacag acttgaagca gatagtgaag 480 tagatctgtgagaggttcta ggtacttagt gtgtagactt tgacgaatat ttctcaagtt 540 gggagcccttgttaaaaatg atgtttaagg gagtggttgg ggggaagatg aaggcatgga 600 ggaggaagaagagaaggaag cccttgccat ataaaattca tgcagactaa acagtttccc 660 tgacagaataaataaagtgg atgctacccc actccagaat caaaagcaat ttaattaaag 720 tctcttaagttgtaaagagt tttaaatgat ccgtgttgaa ggcgaatsct gcyaaatgca 780 gtgggtctgacgtcagctgc cgggcctggg ctgggaggcc atttgctatt ctgtttaagg 840 caggctggattgtcttattt tggaaccagc ttggtggggg gtttgctttg ctactgcttc 900 tgagccctgagcttcaaagg ctgaaattaa tggtgaacaa aattgtgcgg ctctggccat 960 cccatgcgggcaagcccatt gagggttatc attaagtaaa gaaataaaga gggggaaaaa 1020 agcctgcctgttccaaaaac ctcatcagat aatgacctca gtgattgggt tttcattacc 1080 aaacagcatccagagattat caacccatag aagaagggag gggaaaaaaa aaaaaaaaaa 1140 aaattc 1146108 775 DNA Homo sapiens 108 tcgacccacg cgtccgaaaa aggaaatgat acatgtcttgacatttctat tgcagtwtta 60 catcttaatt tctaagggca aaggtgatgt ttcccagttcgtaaagtctc gagagtacta 120 atgctatcaa aagtaattaa tttcaagtgt aaataagaccaaacaaaaac gatcagatgc 180 gacattgtct cataaacatg atagactatt aaatcactttgtgttttttg gaaacagcta 240 taactattaa tatatacagt aatctagtaa atttccttcagatatgctat tgcggataca 300 acagatcatc tattgtcaca agctaaccat tatcctaacaaaatggcgga atacagcaag 360 acataagagt aaaaagaaag aagatgagct gatattaaaacatgaacttc aattgaaaaa 420 atggaaaaat aggttaatac tcaaaagagc tgctgcagaagaatccaatt ttcctgaacg 480 aagttcttct gaagtctttc ttgtagatga gactctaaaatgtgacattt cactgttacc 540 kgaargrgca atattacagg tttgtatgaa ttcagtatacattatatact ataatctgcc 600 aagtgtggtg gtgcatgcct gtaatcccag ctgcttgggaggctgagaca ggagaattgc 660 ttgaacccag gaggcagagg ttgcagtgag ccgagatcacaccattgcac tccagcctgg 720 gcgacaatag caaaactcca tctcaaaaaa aaaaaaaaaaaaaaaaaggg cggcc 775 109 911 DNA Homo sapiens 109 gaattcggca cgagacgacaatggggaacg cggtgtttcc cacctcttgt gggtagaaag 60 cagtctgctt tgaggaggcgagaaggcaaa gccagggcag ggcgttgctg tgggaagcgt 120 tcggtgaaag crggtttcgacgcttaggag ggccgaggga gaagattcca ccagcattgt 180 ccttgcttca agttttaggatgtctgaact ttcagctttc atgttttcaa ccatcatttt 240 tttaatggca caacctacatcttgttttta aaagaagtag cctcaaatta aactcctaaa 300 ctctgatgcc ctggggatgagaacaactag ctkggatctc gtgccgtgta atcaatgttt 360 cattccgctg cctccatcatgtaatagaat cgcttccaga aaggcagtta actggaagca 420 gcagaggctc ccagccgtgagaggactgct caacaatgcc ccccatcgcc gcccccccac 480 ccctcgcacc ccttgtgttttcccctctga ggggcccaag ggttatggct ttcatgtcta 540 ggtgtgggga cagaggagggagaggcagat ccygggccgg gagaggatgg ccctggtctg 600 aatctggagt aattaatgcccacccaaaga aaaggccctg cccaggtcca atgttgtctt 660 agatctgatg atgctgctatttacaaaaca ctgatcgtcc gaaagcttga atctgttcct 720 cctcgaatga ccctgtagatgcctgacctc caccgtacct ccacatcact attcatgtcc 780 ttctaggaaa atgtgcacatgcctcacgca ctatgtggga agggcgtgtt tttaaattaa 840 taaagtgtgt caccattagccatamraaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 900 aaaactcgta g 911 110 456DNA Homo sapiens SITE (456) n equals a,t,g, or c 110 gaattcggcatgagctttct ttctcctgca ggcattggaa atacagtccc agctggcaac 60 accagccagcagcacagccc ggaatcctgc tcctgacctg caccatcccc accagcccac 120 gatagaacgtttttgtaggc attcctcctc atgggagagg atagagtaca tgcgagtttt 180 tgctctcctcccaccctttc acaagagcac tgtgctttct tttcttctct ttttcctttc 240 tttttttttttttaggcagg gtcttgctgt gtcasccagg ctggaatgca gtggtgcaat 300 catagctcactgcagccttg acctcctgga ctcaagcaat cctcctgcct taacctccca 360 gctactcaggagaccgagac aggaggacca cttgagccca ggaggttgag gctgcagtga 420 gccgagattgcaccactgsa mtccagcctg gggaan 456 111 554 DNA Homo sapiens 111 gaattcggcacgagcctcca cctcccaggt tcaagagatt ctcctgcctc agcctcctga 60 gtagctgggattacaggcgt gcaccaccac acgttgctat tttttgtact ttaagtagag 120 acggagttttgccacattgg ccaggctggt ctcaaactcc tgacctcaag tgatccaccc 180 accttggcctcccaaggtgc tgggattaca ggcatgagcc actgtgcctg gctccattta 240 caactatttctatcattata atgcaggggc tctcaaacct gagcatgcct cagaatcccc 300 cagagggctgtgcgcacaga ctgctggacc tttccccagc ttctgattcc gtccctccag 360 agtggggctcgaagattgcc tttgaggtga rgctgcgggt cgggggcacg tctgagaact 420 gctgcagaggtgartgctgt ggctctgtct gcattccccc tggaagactg argcaccagg 480 tgtgctggtgctaacagacc acaagtccct cctggacact gcccttctct gaagggagct 540 gcctcctcactcga 554 112 722 DNA Homo sapiens SITE (2) n equals a,t,g, or c 112gnaattcggc acgagaaaaa tttacgggta acactgaggg gtggggtgga aagttttgat 60cataaagtgg tcaccaacaa gggcacttct gaggtgctaa tgatgttctg ttttctgatc 120tgggtcgtgg tgacattcac atattcatta aattgtacat ttgttttaca taagtttatt 180atatttccta attttaaaaa agttaaaagg aggaggaaaa agttggttat gaaagtgtaa 240ccattcttcc aaaatatcaa ttaaaacaca tctgaattaa gaggtaaaat atatcaaaga 300ttgacagaaa acaaaagctc tgaaatgata tttccagcct aagaacagtc gttgcttttg 360ttggtttagg aagttttgtt ctcctgaact aatgttcaaa atgaaaaaaa gtcacctggg 420ccaggagcag aggcccacac ctgtaatccc agcactttgg gaggccgarg tgggtggatc 480acaaggtcag gagatcgaga ccatcctggt taacgtggtg aaaccccatc tctacaaaaa 540tacaaaaaat tagctgggct tagcggtggg catctgtagc cccagctact cgggagattg 600aggcaggaga atggcatgaa cctgggaggt agagcttgca gtgagccgag attgcgccac 660tgtaccagcc taggtgacag agcgagactc cgtctcaaaa aaaaaaaaaa aaaaaaactc 720 ga722 113 931 DNA Homo sapiens SITE (930) n equals a,t,g, or c 113gaattcggca cgagaaccag atgtttttcc acacagaatg ctagttcttt aagacacagg 60ctgggtgaca tgtttcctta gagtgacaat atttccttat agtgacattt tccttgactg 120gctccatgca gaataggagg atatagaata ggaggagaag gtttctgctg tggcacctgg 180agtggtactt ggtgcacgcc aggtgctaga caatgtgtgt gacaaggatg cacgtgaaat 240gccccccccc gagtgcctca gtgactgcag taaagtggcc cttgtcatgg tcctcttcct 300ctttctgcat cagtcttcat gctgggcggc atgaagagag aaacaaaaac cacctttctt 360gccagggtct tagtaccatt tgctgctctt atctttcaag taagggagaa catctaagaa 420acttatcacc gtattcattc tagactgtta gggrtttaac tcttcaccta cttccctgag 480tggtctgggc tggargttca gagctaartg ggctgggtgt aaatcaggat tccgtccctc 540amtagctgtg aggctgtggg taattcactt catctctctg agccttcatt ttctcacctg 600aaaattgggc atgctaatac ttttccatct ccttcccagg gttcacagga ttaaatgaaa 660ttattaacac aaagttcttg gcctggtagg gggcatgtac gtggccaccg tcctggtgct 720ggacactggg gtaagagttt ggaagctatt ggctgggcaa ggtggctcac gcctgtaatc 780ctagcacttt gggaggctga ggcaggtgga tcacgaggtc aggagattga gaccatcttg 840gctaacacgg tgaaacaccg tctctactaa aaatacaaaa aaaaatttag ctgggcgtgg 900tggcatgcgc ctgtagtccc atctactcgn a 931 114 588 DNA Homo sapiens 114gattcggcac gagatcaaaa tggccagttc tgtgacagta aaagaggttt gtgtcttatt 60taatcttttg ataataataa cagctatggt gtatcacagc tttaccaagt accagacact 120gttctaaggg ctttgcatgg ttcactcact ccttacgtca tccctcggtg gcaggtgctg 180taattatcct tatattgcag acaaggacat tgagacagag gtcaagccac cttcccaagg 240gcacacatgg catctgcact gctcctgacc gaccgacaga gagagctgct gtcacgatcc 300tcaaatgagc tatgcatgtc aaaagtttaa aaataaaaaa gataaaaaca tgcacaaaat 360ttaaaaagta aaccatttca agctggacag actaaaactg agagatggcc agagaagagt 420atgaaagata aatctatgga cagagtaaac cctgactggc ttgaaattag ggcccttact 480cctccacact cctgacgggt tggttcaaga ccargaawta gaagcmcmtt gtgagttcta 540cgstgctgcc ctgggaaaca cacaggctaa acacacccac aggctcga 588 115 812 DNAHomo sapiens SITE (443) n equals a,t,g, or c 115 gaattcggca cgagtatggcccttctttgg cttctgggta tttaaaaaga gctcttggga 60 ctcttctgag gtcttcctgggagcagaaca gtacacatgg tctggaattg ggttgcatgg 120 aataactttc aaggaaagccactgaataaa gtgccctgca ttcctgtcca ttggatactg 180 ataatgctat aagatgatctttctcttctt tattttgttt gagattattg tgactctctg 240 gctaactcct acttatcctcaggccttttc tgaactcaca attcaaatta cagctccctt 300 tggttctctt ccacagcagttgtacttaca tatgtctatt atataattat gaattgtttc 360 atattgtcgc ccttacaggtaaactaatga atttggggct ccatctgttt gctcaccact 420 tgatcctggc agtagcacacaanggctgct caatacctat ttactgaatg agcaaakgga 480 ctggaccact tttagagactggagtatttc cttawaccak gtgagattga wttttgagga 540 cagtttacca ctggaagcttttgcagaact aaggtcattt ttacagtata cataacctct 600 gctgtgtttg ttgatactgtaagtttacat tttcttatga ctctttttaa gtagagcacc 660 cctgtgttta ggaaagctagagctattgtg atgcctttga gtttgcttgg ctgattgctg 720 ggacttgaac tactgagcttatctaaaagc ctcagaggcc ttgtagcctc tgtcttttag 780 agagtgtagg taaaggcttgttttccctca aa 812 116 506 DNA Homo sapiens SITE (13) n equals a,t,g, orc 116 gaccatgatt acnccaagct cgaattaccc ctcactaaag ggaacaaaac tggactccaa60 cgcgttggcg gccgctctag aactagtgga tcccccgggc tgcaggaatt cggcacgagc 120acctcctgag gaatatggtg taggaaagcc acccgcgtgc tttctggctg ggatggctct 180cttccttggc tgctggaggc actggagaga ggtctgataa ggatggctgt atggatcagt 240gggtcttatt cctcattctg cagcagaagc aactgggatg ttttttctcc taatattgtg 300ctggcttctc tgcctttctc tttccggtct gtatccaagg ctgctaaacc ctggtggctg 360gctctccctg ctctctttcc agatggatta tggctggatt ctgccatggg gagcttgtac 420agtcagacat ggaaagccag gaatgggaaa gaggtcaggt ggttctctcc cacacctcac 480tgccttggtg ctatgtctca cctcga 506 117 751 DNA Homo sapiens 117 gaattcggcacgagagcctc gcaggtggat tagacccacc cgaggctcgg gagaaaccac 60 ggcaccttgttgttttgagc cactaaatgg cgggacgctt gttcacgctg ctgctatggc 120 aagagctagcgaggcggctg gtaccgggtg atgcttcacc acggctttcc agaaagcgct 180 ccgtgaccccaggcccaccc ttcccgacac tcacggttcc ctcagaaatg ctcctctcaa 240 atctctcactctccctgcag cctttgttgt ttcttttttc tttctttctc ttttgcaaga 300 tgggatcaaggaaaggtctc agacacaaaa cgcaacattt ttcttccatg acagatcaga 360 tattgaagggctcagtgagg agccctgctc tgggacaact ccatgattag cgctccaaga 420 ggcagtcacagggaagcagg tgctctgttc ccctcctggc tcagcaatcc cgcagtcctc 480 ccgtcccgctccaggcccag ccagcctggc tgcttggatc cgagacaata gcttggtctg 540 gaggcggctcagggtgggag ggacccaggg acccgggcac cagtacagca gctgggaatt 600 caggcccagggatagggatg gggcacagga caccaccccc atctcacaca gggagatgaa 660 ggtgggatccagcatgggga ctggacatcc ctgagtccag ctgccccgtt acaatggggg 720 aactgagatccggggatggg atagttctcg a 751 118 960 DNA Homo sapiens SITE (460) n equalsa,t,g, or c 118 ttttgtctag tacatatatg taaatatatt aatgttgttt ttgtgtttgtgatgtagtaa 60 ggagatgtac atagaaattc attgaggtat atagatactc atctgtctaggcagttccca 120 attttctgaa gaatgtttta cagcaaaatt ttctattttc ttttattaaatagtgacacg 180 tcaaacaatg tcacatccaa aacactagtt tcatcaattt ctagcagtaataatagactt 240 gctgtaagta ttgttttctg atgccatacc cttgtcatac atattattaaatgaccaata 300 ttatgtatga agtagacaaa aaaatttact caaacttcat tcaaatcctaattgtgataa 360 tttttgtttt atatttaatt ataaaccaaa atacatttgc atttttaagctaatttgtct 420 caaaattttg ctttatattt ttggatcagg ttaaagtccn gtggatcccctgaatgttat 480 tgtccctctt gatggttttt acttctgagc tatacgtcaa aagacacataagcttcaaaa 540 gtcmagacaa acctcattgc cataaaaatc aagatataga tgttctgttccgtaaactcc 600 ttgaaaaaca ttttaaagtc atcaatatga tctgtttccc atgaaacttaagttagcttt 660 cttattggag twattycttt tctgtaagtc tgaaaagtag agattttgttttacgcattt 720 tagtaacctg caacaaccaa ctctaaaaaa gatttggctt gtaatgacggtctctgcttt 780 tttgggtttg gagtacacaa ttgtaatatt tacttagtta tttgtgtttttctttgttca 840 aggtattgac tagtttcata aattttttgm aagtttttct ttcattggttggaaagcaga 900 ttacattttg cactattaaa ataagtttat tactttaaaa aaaaaaaaaaaaaaactcga 960 119 1442 DNA Homo sapiens SITE (1377) n equals a,t,g, orc 119 cttctatatt agatggacag atttatatac ttttccatgg aggattaagt aaactgaaac60 ctaagacaca cgaagaaatt ctaagtggaa aggccactta ttagttagtt tacagcagta 120tcgtaagtga caggatgata ggagtgtggt aagtgatcag gataataatc tgcttagtaa 180gagaaacaat ttgaatttta gaaggaaatt gccttaccat ttgcaaatta aggtaattaa 240aatacagtga atttcaaaat gcctttttaa tgacaatgtg tgaacttaat ttgttttaat 300aaaccaaaat trttgttatt gtgttaaggc tattttacat tgaatgtgta tcttgccact 360gatgttaact tatcccatct tacccaaggt tgtaggtaac aatatactat tgggtgacag 420tggactaaca tctctagtga tccctttgtc agtggtcttt aacttaaaat aatttagaga 480atatggtttc tacaacttac atttttgttt wcttgtaact acagattatt atgatggttg 540taatgaagat tatgagtata attggagcta tatgtttctg aattctgaac aactatttat 600aaaattttat cctacttttt tctgttgaac atatgacttc tctggtctgc taaacacata 660cagaccttta gttttggttt acatggattt aaatatatag atatatcact gtaaaataaa 720cttcaggtgt aacagattta tagagaaagt aatcatattt gtttatggtt gtgtacctac 780tttgagaaga aaagaaaaat attagaatga acagataatt ttacaagtgt tgatcactta 840ccagcaaacc agaaacttca gagattttga aagcaaatct attttctctg ctgtgtatta 900aattcattta tctaaaatgt tattgctcct ggcttagaat catcttgtgc aaattctctt 960tttttgttgt ttgtctgttt gcctgttgct caccatagac ataattttct tttcataaaa 1020cattctttgt ataatcacct cagagattat gaaagtgact ttgataaaat ttaatggtgt 1080tcacaaaata attttcacgt gagtaatttc acagtgcgtg tattgtatgt tatttagtgt 1140attttatatt ttgtttcaat tagagaatgc tattgaatcc agtttttgtt tagttactgt 1200tcattttact ttataaaatt gacataattg agtttattaa atttattggg ccaatttaag 1260taaacagttg aacgtttcat aagtcatgag gtctttttgg gcatatacat gaagtaaaca 1320aagacaatac taggctatgt aataggragg ctaccttaat taggaggtaa atattcnttt 1380tggaaattgg gcccgtgggc ctcgggtgga aaatggggna atatccctag gtaaaaaaat 1440gg 1442 120 845 DNA Homo sapiens 120 gattttacac agaacatatt ctctgcatgatttcagaaaa gaaaatctaa aaaggtaata 60 cgggtatttc aaataaaatc ctttctggtatgaaaggctc cattgatttt attaagcctt 120 cctttacctt gtagtacaag gtgctttaatgggatagaac taagcatatc aatatctata 180 actgcatttt gtgctagaca attactgttcttttctctaa aatgtatatg tcaatttaca 240 aggccaggga tagaaaacac tccataattgctttccttga ttttgctgag gatttggtat 300 gattttagta agcaaactgt tttttggtttttccttaatg tttttaattt tttttcctct 360 tgcaacaatg acggtgcatg ttcttataaatataggaagg tccagatata aatagtaacc 420 taaagttctt gctgtgctta aaaaaaaaaatcatgtggcc ctttcaatat ttgaactgct 480 aagcaatgac atctgtagtt ttatctccttttttatgtca tagaaattaa tatgatactt 540 taaatatgta aatataatac attaggtaatgctattattt atatctgtct taacataatt 600 taagttgtag ctgtgtcttg gaaatatttttaaggtaatc tatattcaca ttgcctgtgt 660 taatgctttt taaagtttgt atacatcagatgtatatttt tggtttggca taagctacga 720 ttgtaatttt tcttggcttt ttgttcataaagaatttttt gaaggaatgg taacaaatgg 780 taatttacaa atggttgtga ataaacacatttttacactt aaaggwaaaa aaaaaaaaaa 840 ctcga 845 121 360 DNA Homo sapiensSITE (340) n equals a,t,g, or c 121 gaattcggca gagaatcagc atgtctatcacctcaaatac ttatttcttt ttattgggag 60 cattcaaaat cctctcttct agctattggaaaatacacac taaattactg ttaactatag 120 tccccctgca gtgctgcgga atgccacaacttatccctcc tctccagctg tagtttagta 180 tccagtaaca tactcttttc atttcctttctttgggcaga aggctagatg ttgcctgttt 240 ttgttttatt tttctgcttc acatatagcgcacgaaagca gagtgtattc aaaaaaggaa 300 atgtgtttga aaaaaaaaaa aaaaaaactcgagggggggn ccggtaccca attcgcccta 360 122 944 DNA Homo sapiens SITE (932)n equals a,t,g, or c 122 tcgacccacg cgtccgccca cgcgtccgga cagacccagcctggagctgg cccctggcct 60 gtgtgctgac ttcttggggt cctcaaacca ctgtatttttctgttgagcc tgtacttggg 120 gagagatcag tagcatttga ggaagtaaga gaaaagaatcatggtacctc agggtttctt 180 tccctttact cgctggcagc cattgtctgt gggcacctcatgtttttcca cactctactg 240 ggccgtggag gtaacgatca cccaggccag tctcctctgcctgggatgcg ccctctgaga 300 ggaggcctag cagggcaggc tccctctggg catccctggatgcagcctct ggacacatgc 360 ctcctttaaa gtgtccgggt gcagctcagg ttgagtggaggtagaaggag aaacagacat 420 gtttaccacg cgttttccaa agctcctgat ctttcccaagattgtaactg aaaactgctg 480 tctcttgttt tgttcgtttt gggggtggtg gtgctggctgggccatgctt gtgaagtgat 540 gtgtgtctct gatttaacgg attcactgtt ttctctgctaattgagagag cgttatttac 600 attatttatt tgttttgaca caagtgcttt cagtgttttatcctagctaa tggcttctta 660 aaggtaataa aacccttcca acgtaattgg tcagataaaactttttttct tgtatgctta 720 aataaagcaa ttagtgaagc acttctatcc aaaatgacttttttgtcctt ttttaaaacc 780 aatttactgt tactggaaac tttttgtaca ataawgcaatcacgcagatt aaagaaaaaa 840 aaaaaaaaaa aaaaaaaaaa aagggcggcc gctctagaggatccaagctt acgtacgcgt 900 gcatgcgacg tcatagctct tctactacgt gnaccctaactncn 944 123 914 DNA Homo sapiens SITE (909) n equals a,t,g, or c 123ggcagagcaa gagatgactt tagatgagtg gaaaaatctt caagaacaga ccagaccaaa 60gcctgagttt aacatccgga aaccagaatc cactgttcct tccaaagccg tggtgattcg 120agagtcaaaa tacagagatg atatggtaaa agatgactat gaggacgatt cccatgtttt 180ccggaaaccc gccaatgaca tcacatccca gctggagatt aattttggta acctccctcg 240tcctgggcgt ggagccagag gaggcacccg gggaggccgg ggaaggatca ggagggcaga 300gaactatgga cccagagcag aagtggtgat gcaagatgtt gcccccaacc cagatgaccc 360ggaagatttc cctgcgctgt cttgaaagag ccctgtttcc cagcaccgcg gagctgcact 420gcacacctgt ggggagactt ttccagctgg gccaagggag tcagactcta agaacaatag 480atgttgcttt tcccgtgtca tgtaaatttg ttgcactttt ttgggctgag ctgttagagg 540ggcttctcca gaggctcgag agcaggccat ttcccaagaa gatgaagaat ggtgactgtg 600tttttattga aggaatttca aatgaagaat aatgtttaaa atgtgtatat agagatagta 660tagactcctc cgcggaagca tggagggaaa ggaggttgta aaatagactc catggagact 720cttaggaagc agtagattcc cgggggctgt gcctttagcg ttagaggaaa cacatagagc 780tggaactgtt aatggaaagc agtcacagct gagttttcgg agaccaagaa attaaaatac 840aattgcactt acaaaaaaaa aaaaaaaaaa aaaaactcga gggggggccc gtacccaatc 900gccttgtgnt gcat 914 124 462 DNA Homo sapiens 124 gaattcggca cgagctgggctcaagtgatc ctcctgccga ggcctcccaa attgctggga 60 ctgcagctgt gagccaccatgcccagcctt aacttggttt taagacctct gatttgcctt 120 gcctcaatta cctcctttcttattttcttt cctttgttga ctctcatact ctgttctcct 180 aattctcccc cttttccactccctgcccac cctgaaagac acacacacac acaataagtg 240 ggtggagtaa gaagtcaacggagttggata taagcattcc tgcttttctg acatctccag 300 tgtcttggag aacaaggattctagaatgag ggctcctcat tatgcttcct ttcaacattt 360 tttctctgtg ttacttaagctttcacccca agcatgtttg acagagagcc agtgcattcc 420 ccttactttt tacaaaaataaaaaaaaaaa aaaaaaactc ga 462 125 545 DNA Homo sapiens SITE (7) n equalsa,t,g, or c 125 tcacttncgg ttccgntcga tgtggtgtgg attgtgagcg nntacaatttcacacaggaa 60 acagctatga ccatgattac gccaagncga aattaaccct cactaaagggaacaaaagct 120 ggagctccac cgcggtggcg gccgctctag aactagtgga tcccccgggctgcaggaatt 180 cggcacgaga ttcgctgcct aattccacca tgatgtttta ctatgcatgctttatcttat 240 actcatctct ctctcctctc tctctttctc tttctccctc cctcctttctctattataat 300 ttagtcatct tattttttga ggcatttcag aatatatcac acttgtcctaaatacttcag 360 tatgaacatc attaactaga atttattctt tgttttactt ctgatgtgaaayttatataa 420 atacaacatg ctatgaattt gttttccmaa aaaccaatca acaatttawtaagcatggka 480 acaaaaaacc tgaaggcttt atcttttaga gtagtagttt ttaaaaaaaaaaaaaaaaac 540 tcgta 545 126 912 DNA Homo sapiens SITE (906) n equalsa,t,g, or c 126 gaattcggca cagagaaaca tttcatcccc agtaagattc ctcatcgtcattcacaggtg 60 atctctgttc ccaccctagc cttggacaat tctgcatcta ctttgtagctctataaattt 120 gccttttctg gacatttcat gtaagtcgat cacacagtat gtgttcctttgtgactggct 180 gcttttgctt agcatgacgt tcttggggct cgcaacgcag cttgtgtctgttgttcattc 240 cttttgcagc agaatcgtat tctgttgttt ggatgggcca cctgtttgttgtctgtttac 300 tctccagctg gtggacattt aggccgtttg cactggcggt tactgtgaatcatgtcgctg 360 tgaacattgt gtgtgtgtct gcgtggactt gtgtgtcctg ttctctgggaaggagttgcg 420 ggttagargg tagttttttg tttcccctgg agactctctg gtttccacatatggtagttt 480 tatgcttaac cttttgagaa attgccaaat ggctttctga agtggccacgtcattttgct 540 ccctccagcc gtttgtaatg ttcccatttc tcctatgtgt aattttaatacaaagcagta 600 aaaagttgcc attatggacc tagtaaattc tgaggtaaca taagagagaaataatgatgc 660 agccgtcatt actgtgctgg taatgtaagt ttcctttttt tttgtttttaaatggagctt 720 tgcagagatc aagtcgagag aagaacactg ggccagcctg actccaaagcctactctctt 780 aagcgctttg ctgacttgtg atgttttaaa atctagcatt attttcaaatgctgtgagag 840 cactgaagat aaaggatttg attctttttt tcaggcatcc aaggatggttcatcatcaag 900 aatcanttta at 912 127 1048 DNA Homo sapiens SITE (13) nequals a,t,g, or c 127 gatcccccgg gcncgnngaa ttcggcacga gggacagagtagttccagag gcagttctca 60 ctgtgacagc ccttcgccac aagaagatgg gcagatcatgtttgatgtgg aaatgcacac 120 cagcagggac catagctctc agtcagaaga agaagttgtagaaggagaga aggaagtcga 180 ggctttgaag aaaagtgcgg actgggtatc agactggtccagtagacccg aaaacattcc 240 acccaaggag ttccacttca gacaccctaa acgttctgtgtctttaagca tgaggaaaag 300 tggagccatg aagaaagggg gtattttctc cgcagaatttctgaaggtgt tcattccatc 360 tctcttcctt tctcatgttt tggctttggg gctaggcatctatattggaa agcgactgag 420 cacaccctct gccagcacct actgagggaa aggaaaagcccctggaaatg cgtgtgacct 480 gtgaagtggt gtattgtcac agtagcttat ttgaacttgagaccattgta agcatgaccc 540 aacctaccac cctgttttta catatccaat tccagtaactctcaaattca atattttatt 600 caaactctgt tgaggcattt tactaacctt ataccctttttggcctgaag acattttaga 660 atttcctaac agagtttact gttgtttaga aatttgcaagggcttctttt ccgcaaatgc 720 caccagcaga ttataatttt gtcagcaatg ctattatctctaattagtgc caccagacta 780 gacctgtatc attcatggta taaattttac tcttgcaacataactaccat ctctctctta 840 aaacgagatc aggttagcaa atgatgtaaa agaagctttattgtctagtt gttttttttc 900 ccccaagaca aaggcaagtt tccctaagtt tgagttgatagttattaaaa agaaaacaaa 960 acaaaaaaaa aaggcaaggc acaacaaaaa aatatcctgggcaataaaaa aaatatttta 1020 aaccaaaaaa aaaaaaaaaa aagggggt 1048 128 722DNA Homo sapiens SITE (251) n equals a,t,g, or c 128 gaattcggcacgaggaaagt ttcaaccctc tgacatgtgg gttcagctta tttttttctt 60 tgttcagtatggagactctc ttacttctgc tttttttcct ttctcttcta atttttcgct 120 tcagaattctggtttctcaa tgcataaact gaagtaattt cttccattct acttttctct 180 gccccaggcttgagatagaa ctagggagcc cagtgaggcc ttttctttcc taaattaaca 240 ggcatctgtgncataaatgc tacctttgaa ctatgtgatt taagataatg tgcagaagta 300 cttctctggtctttcaggtt gcytgcataa ctawgtactt ggttgaactt gtaattcttg 360 ctgacaacagtcctgctgtt ttccagtaag gttcgtgatc ctcgggccaa ttttgatcag 420 tccctacgtgtactgaaaca tgccaagaag gttcagcctg atgttatttc taaaacatct 480 ataatgttgggtttaggcga gaatgatgag caagtatatg caacaatgaa aggtaaagaa 540 attgaaaaatgaaaaatctt tcccatgtaa tttgagtaat agccaggaac ccactcactt 600 tgaaggcccttctaagaaca aagaaaagta tatggttata gatggcagca tgaaaaggaa 660 accaacttgcacatgcaccc tcaaatctaa aatacaagtt aaaaaaaaaa aaaaaaactc 720 ga 722 129477 DNA Homo sapiens 129 gaattcggca cgaggtgagt atggcttttg tcttccatcttgctcagggt actttggaac 60 cgctatacat tgcaggagct tagcttctgg ttaccatggtttgcttccag agcaacaagc 120 ctagtacttc aacatggaga caattatctt ttgtttttgttttgttttgt ttgttttgtc 180 ttggccatgc ctttttgagt ttaccttttt atattttgtccatcattgcc atgtgtttgg 240 agcagtgggc gttccataac atgaactcac tgtaccatcacgaatgggaa gtaaggggaa 300 accttatcca tgtggatttt actcttccct gattccctaaattgggtttg caaaatacta 360 ctgtgcactt tcttgatgat tcgggcttat ctttatgactgtctgtkttt gtgtcagact 420 gtaaagaagt ataaaagtct ttagcttgaa aaaaaaaaaaaaaaaaaaaa aactcga 477 130 1296 DNA Homo sapiens 130 ggcacgaggccactggaatc tgatcctgat tgtcttccac tactaccagg ccatcaccac 60 tccgcctgggtacccacccc agggcaggaa tgatatcgcc accgtctcca tctgtragaa 120 gtgcatttaccccaagccag cccgaacaca ccactgcagc atctgcaaca ggtgtgtgct 180 gaagatggatcaccactgcc cctggctaaa caattgtgtg ggccactata accatcggta 240 cttcttctctttctgctttt tcatgactct gggctgtgtc tactgcagct atggaagttg 300 ggaccttttccgggaggctt atgctgccat tgagaaaatg aaacagctcg acaagaacaa 360 actacaggcggttgccaacc agacttatca ccagacccca ccacccacct tctcctttcg 420 agaaaggatgactcacaaga gtcttgtcta cctctggttc ctgtgcagtt ctgtggcact 480 tgccctgggtgccctaactg tatggcatgc tgttctcatc agtcgaggtg agactagcat 540 cgaaaggcacatcaacaaga aggagagacg tcggctacag gccaagggca gagtatttag 600 gaatccttacaactacggct gcttggacaa ctggaaggta ttcctgggtg tggatacagg 660 aaggcactggcttactcggg tgctcttacc ttctagtcac ttgccccatg ggaatggaat 720 gagctgggagccccctccct gggtgactgc tcactcagcc tctgtgatgg cagtgtgagc 780 tggactgtgtcagccacgac tcgagcactc attctgctcc ctatgttatt tcaagggcct 840 ccaagggcagcttttctcag aatccttgat caaaaagagc cagtgggcct gccttagggt 900 accatgcaggacaattcaag gaccagcctt tttaccactg cagaagaaag acacaatgtg 960 gagaaatcttaggactgaca tccctttact caggcaaaca gaagttccaa ccccagacta 1020 ggggtcaggcagctagctac ctaccttgcc cagtgctgac ccggacctcc tccaggatac 1080 agcactggagttggccacca cctcttctac ttgctgtctg aaaaaacacc tgactagtac 1140 agctgagatcttggcttctc aacagggcaa agataccagg cctgctgctg aggtcactgc 1200 cacttctcacatgctgctta agggagcaca aataaaggta ttcgattttt aaagataaaa 1260 aaaaaaaaaaaaaatttggg ggggggggcc ccgtta 1296 131 738 DNA Homo sapiens 131gaattcggca cgagtgacaa gaaagacggt gtcagatgca cattaatctt tagcctgatg 60tccttcatga tgtccaacct ccagtttcat ctcctgccac actcatcccc catacttcca 120ctcttcacac tggccttact caaaatgcag attccaggac tcaggctatc tcactgcctt 180cttacttaca attcttatac cagaacaccc ttcctcctcc cctcatctga atcttacctg 240gtttttgaaa tttaagtcag ggccttctta ggaagatttc cctgattcag atccaagttg 300aattatgata accctccttt ggctcccata aaatcttata acttcctaac tgtgttttat 360gaatagttgt ctagtttagc actatgtcag gagctattga cagcagggct gggcacagtg 420actcacagct gtaatcctag ccctttgaga ggacaaggtg ggaggactgt ttgaggacac 480ctcaagccca tccagcctag gcaacagaat gagatcttgt ctgtacaaaa aaacaaaaga 540ttaattgggc gtggtgacgt gcacctgtag tcccaactac ttgagaggct gaggcaggag 600gattgcttga ccccaggaga tcgaggctgc agtgatccat gatggtgtca ctgcactcca 660gtctgagcaa cagagcaaga ccccaccccc caaaaaagct attgagggta gcagtttact 720ttcattgctc tacctcga 738 132 442 DNA Homo sapiens SITE (306) n equalsa,t,g, or c 132 gaattcggca cgagtgaccc agaagggtga gtcagttggt agtgtggggtgcatgagggc 60 cattgcaggt tttgataatt accctttatt ttaatttgat catacttttttgtttataac 120 cttattctaa aaataattca aggtgaccat gcttccatta tacttcttgcaaccatacct 180 atctttggtg atatttatta tgttaaggga caattggcat cttttggcccttacctgtag 240 ctattctatc atctggagat tatctccaga cacaaatcca tcgcccattgctccatcgag 300 gcacantcag ctckttgtag ttgccattgc ccctctcgag ccttctccacatagccacat 360 gcaatccatt cccaaaaacc tagctcaatt ttcctcatca cagatgttttccctgaccct 420 ccagttggta tatatctcct cc 442 133 882 DNA Homo sapiensSITE (881) n equals a,t,g, or c 133 gaattcggca cgagatgttt tcttcactcaaaaaatttta tattctcaaa catgtatatt 60 ctttccctgt cttgttccat tttcttttcttttttctttt ttctttttcc tttctttcgt 120 gggctgagaa aggggcaggc aaaatgaagctggccactga aaactgtaag atggtcaaaa 180 gctgacagcc tgtgtatgtg aaaagggaattgtaaatgga ctgcaatgta atgtacactg 240 taatttgaat acaattactg tatctaaaaggagctgctat gaagtacctt tcttatgttg 300 ctaggctact gtttctgaaa gccctggatctctttgcacc aaaaatggtc cagatagact 360 ctttttaagg atcttggctg ctttttactagaaggttgct tttatgagca tatttatact 420 gctgaaggat gagtgttaat tttaattaactttgccgttt tgtagagaaa actattccac 480 aagataaatt ccaagtcttt tcacctgtcaggcatgcata ttttaatatc tgtttggata 540 gtcagaagta gaatcataaa ggtaaaatatgagttgttac tttgtttctt cgatgtcata 600 ttttatgtgt aatatatatg taaagggccattcttaagtt ctctccttaa acttaatgct 660 gtcaagtgtt agatgtgtgc atgtgaacttgttgcactgc agaaacatat tcagagttta 720 tctatgtaac ttattcactc tgtaaatacatttaaagttt ttgtgatgta agcttaattg 780 atattctgtt cagaacttty tttagwctaaaraaagttct gaacagaata tcaattaagc 840 ttacattgat attctgttca gaactttctttagctagaaa na 882 134 1032 DNA Homo sapiens SITE (5) n equals a,t,g, orc 134 ggcanaggga accaccttct gtagaacatt caaccaggcc cagatccaga aggcttgagg60 ccctgtggtc cccatccttg gggagaagtc agctccagca ccmatgaagg gcatcctcgt 120tgctggtatc actgcagtgc ttgttgcagc tgtagaatyt ytgagctgcg tgcagtgtaa 180ttcatgggaa aaatcctgtg tcaacagcat tgcctctgaa tgtccctcac atgccaacac 240cagctgtatc agctcctcag ccagctcctc tctagagaca ccagtcagat tataccagaa 300tatgttctgc tcagcggaga actgcagtga ggagacacac attacagcct tcactgtcca 360cgtgtctgct gaagaacact ttcattttgt aagccagtgc tgccaaggaa aggaatgcag 420caacaccagc gatgccctgg accctccccc tgaagaacgt gtccagcaac gcagagtgcc 480ctgcttgtta tgaatctaat ggaactttcc tgtcatggga agccctggaa atgctatgaa 540gaagaacagt gtgtccttcy tagttgcaga acttaagaat gacattgagt ctnaagagtc 600tcgtgctgaa aggctgttcc caacgtcagt aacgccacct gtcagttcct gtctggtgaa 660aacaagactc ttggaggagt catctttcga aagtttgagt gtgcaaatgt aaacagctta 720acccccacgt ctgcaccaac cacttcccac aacgtgggct ccaaagcttc cctctacctc 780ttggcccttg ccagcctcct tcttcgggga ctgctgccct gaggtcctgg ggctgcactt 840tgcccagcac cccatttctg cttctctgag gtccagagca tcccctgcgg tgctgacacc 900ctctttccct gctctgcccc gtttaactgc ccagtaagtg ggagtcacag gtctccaggc 960aatgccgaca gctgccttgt tcttcattat taaagcactg gttcattcac tgaaaaaaaa 1020aaaaaaaaaa aa 1032 135 1766 DNA Homo sapiens 135 gtkattcaaa gccatcacaaaacactataa gactgaccaa aatttagata acctttgaac 60 cacgattttt ttccacatctgtctgtgaga cacagcgcaa tgctactgcc cttccagaaa 120 ctgtgctaaa aagagaaagtccaaaagact ctaaacaaaa acctcgacgc cgttgaggat 180 gtgtttcatt ctggtggtctgttttgcaag cttgataaca gaatgtccgt gccattgtaa 240 atgttgtaga gatgtgggccgtggcccaac cgtcctatat gagatgtagc atggtacaga 300 acaaactgct tacacaggtctcactagtta gaaacctgtg ggccatggag gtcagacatc 360 catcttgtcc atctataggcaagaagtgtt tccagatcct ttggaaaggt gggcatgggg 420 caggtgcttg gagagtggcgtttgagccag agcgacccca tttcccgtgt gaaccatagg 480 cacaacccag gaagtttccccacttgtagg agtgtgggta ttccagagca agactgtggc 540 caccatcttc ccctcttggtgttttccgaa agtgacagtg ttggtcatcc catgaccact 600 gaagcttagt aaccagcgccaaaaagtaga ttcatcaaac tagagacccc agctcccctt 660 ctcgccatct tctttctcaagttgaccgtg gtgctgtttc tggaaggcat ctgcaactcc 720 aagtccatgc agaactctggaaggccaagt tcatcgcagc atgttcacca tatcccagcc 780 tccaaatcta tcctcctaccttccaacgca tgacctgttg gggagcagag acttaacccc 840 caactcagag gaacccttcctccagcgtct ttggcatggt ttctagggtg agagttccca 900 atttggatag aacggccaccatattggtta ctgaatctct ctcccttgtt tttattacgt 960 ttcctttttc aaactgtccatgggaaggct gaattgagtg actccccaga atgaagatga 1020 gaaggtgaat ataatcaatgccaatgtaat gccagcgggg tgagatgccc gatggagrtt 1080 tcaaagatgt agctagcattttgaaaccat atgggcaaaa cccggcaacc agaaggggac 1140 agataaggac cgttccagaaatcccaactc tcacacccag cccaggctgc agtctccaca 1200 ccaaacagtc aacaaaacacaaaccctgaa ggaaaacctt ttccatacac ccaggctatg 1260 cattgaagag ttttccactgtatacatttt tatccagatg aaggtatttt tatattttga 1320 caataggaaa cagtgaccattttcagagta atcaaatctg gaacaaatga aacatctttt 1380 agccaccacc accctgttgcaattaagaca accgtggggg aacacaccac tttttactgt 1440 tgaaaccaac acaacgttgaaatccaggct tatacgcaga ctccgattcc ctagagaact 1500 aaatttggct ttagtgtgacgggatttgat taagcactta gtatagtctt ttgaacacgg 1560 aaatcctgtt gtacttaaagctagcggacc cgtgaacaac tttgtcaggt tcacgtccta 1620 taacggttma aaracacacacacacataca caaaccgttt ctatgagaga ttgatgaact 1680 ttgtttaaaa ttttaaaaaaaggaacacgt tctgtaaacg agtcgctaaa tacagaattg 1740 tataataaaa aaaaaaaaaaaaaawt 1766 136 470 DNA Homo sapiens SITE (315) n equals a,t,g, or c 136ccgccgccgc cgctacagcg accctgaccg ccgtccgagc cgccagacac ccagagagac 60gccagaggcc gcggaggggc gaagacccgg agtaactctc ccttccaccc caacccggat 120cgccagccct cgagagctct gtgctccacg ccgaggatgc accgtctctg gattggtccg 180gccttcttcc taatgacatc gctcagcgtc tctggagccg tcatcccgcg gaatgggggc 240ccagggggtg tcagytcggg gccttgcctc ttgcagctac tctgtggtca ggccgggtcc 300tccaccatca ggaanatccc atcctgagct ctgtctcctg cccctcctgc tgtgggatgc 360tgagcacaga gcccacagcc catctgcctc ttcacctccc tgaatccgtg tccatctgca 420ataaacgaca gcctcggctg cctcgtgctg aaaaaaaaaa aaaaaaaaaa 470 137 1168 DNAHomo sapiens SITE (1163) n equals a,t,g, or c 137 ctggatctat agactcttcttgccctaaag aatggcatgt ttgcactcct tcccccaaca 60 tgtacagatg cctgtcactcttggtgactt tgctgggctt ctagtccctg cagatgttta 120 agggagcaat gaatggggagtgtggatgca aactacggcc tccttggcac tgtttcagat 180 gggggatttc ccttctctaggagaacctgt gctggaaaag gtgtggcacc cacactgaaa 240 tggggcaagc tcttcccagctttgtggggg cccttggaaa acatccactg agatggaggc 300 agtcttcttc ctcttcttcctcctgctcct cttgacctgg accagcaaga tagcaccaat 360 ccttttctcc tgatggcagtatctgaatga ctttcacagc tgaaggccag agaccagcct 420 acagctggga ttcaggcttcaaagctttgg tgaggatgac tccagaacca ggcaggtagt 480 ccccctccag gatgccatggcctaaagcat ttcactcctc agtcactagg ctgtgaactc 540 attgtggctg acacttttattcgctgctat gttttttagc aatgcccggc acacagacct 600 gcttactatg cttttgctgagtgagtgaag ggataagtcc ctttctgcct ttttgatact 660 cactttggtg ccccttgaggtcacagagac ctggatttga cttctggctc tgccacacaa 720 gagcacggat gctttgggtcagttacttca gctctgagag gctcaattgc ctcacctgtg 780 aaatgggtta gtgattccaggaatcttacc aggccccatg gacagcatgt acataaagag 840 cctagccctt ccctctcctccctctccagg ggccaggcct gactcccctg aagccatttc 900 cttaccattt tgatccctaagcctgttatc agatcttctt tctgatctac caccatggct 960 caaatcttgc ccttcatccttgcctttctc aaagacaaaa acacccttcc tctgctccac 1020 tcagagtgta gcggggaggcttatactgca gtggttaaga gcatatccct ggaattggaa 1080 ggaacagggt ctaagattatgtagatatag cacaaagcct tgctcctgct cgtgccgaat 1140 tcgatatcaa gcttatcgatacngtcga 1168 138 1294 DNA Homo sapiens 138 gatcttgtcc aagcagtcggggctacttcc aagaatgtca gctcctgtta gcaaccagtg 60 gagtctggcc ttgggctctaagttgacctc tctatagctc caaatcctac caatctcaga 120 aaactgtaag aggcacagatgactccacca gctgcagagt gactctgaag agagtcttca 180 cttactgcac aggcaaagaaaggcacagga atatttccta cctctggcac gaggtgagtc 240 ccacctcccc ccacccccatctccaggagg caggtagagc agttctgacc gagaggatag 300 actgctgttg ctgtctttccccagctctga actagtttta aggtagctta ggatgaaaaa 360 tggagaatga ttgggggttccaaaccactt tcttctccct tggcttatat ctcttcacca 420 tttggtggtc aactgtgggcctaccctgga cctcatctac tcagcgagaa ttggacatga 480 agctagaggc agctgccttggaagggaart tcaggctcac ttggacagcc caggccatgg 540 caggaagaat cccttcctcttggggtcctt gatgggcatg tgtgatgggg aaggagcagt 600 ctcccagccc tgggtctgctccccacatct ctcctaattc cacttcacct tttgccaccc 660 cctccccacc agaggcctagcccttttgtc accgaaggcc cccagagtgt ttctgtgtga 720 aaccctctca tttacactgtggcmwcaaaa atccacaaaa gatggattaa ttgcactctg 780 gttaatagca gcagcacaatgattaaaatc tatattccta tcttctctag caccctggtg 840 tggggatggg gcggaagggtgtcttgaggg gcagggagga ccccataaaa caatccctcc 900 tgcattctca ggctaaatagggcccccagt gactacctgt tcttggctgt cccctctgaa 960 gagctctgcc ttctcacagccaccaccagt tgccccactc ccaggaaaac agcacatgtt 1020 cttcttctcc tgccttgagactgcgtgtta gtcttccatt cataactcat cagcagctca 1080 gtccttctta tgtctagtctcagttcattc agccaaagct catttttgtc ctatccaaag 1140 tagaaagggt tcttttagaaaacttgaaga atgtgcctcc tcttagcatc tgtttctgac 1200 tcccagttat ttttaaaataaatgatgaat aaaatgcctg ccctgaaggg ttctggagga 1260 aaaaaaaaaa aaaaaaaaaaaaaaaaaact cgta 1294 139 1720 DNA Homo sapiens 139 aaccagaagt ggacgtgcatgacagtggac ctagaggctg acaaacagga ctacccgcag 60 ccctcggacc tgtccacctttgtaaacgag accaaattca gttcacccac tgaggagttg 120 gattacagaa actcctatgaaattgaatat atggagaaaa ttggctcctc cttacctcag 180 gacgacgatg ccccgaagaagcaggccttg taccttatgt ttgacacttc tcaggagagc 240 cctgtcaagt catctcccgtccgcatgtca gagtccccga cgccgtgttc agggtcaagt 300 tttgaagaga ctgaagcccttgtgaacact gctgcgaaaa accagcatcc tgtcccacga 360 ggactggccc ctacccaagagtcacacttg caggtgccag agaaatcctc ccagaaggag 420 ctggaggcca tgggcttgggcaccccttca gaagcgattg aaattagaga ggctgctcac 480 ccaacagacg tctccatctccaaaacagcc ttgtwctccc gcatcaggac cactgaggtg 540 gagaaacctg caggccttctgttccagcag cccgaacttg gactctgccc tccagatcgc 600 cagagcagag atcataaccaaggasagaga ggtctcagaa tggaaagata aatatgaaga 660 aagcaggcgg gaagtgatggaaatgaggaa aatcagtggc cgagtatgag aagaccatcg 720 ctcagatgat agaggacgaacagagagaga agtcagtctc ccaccagacg gtgcagcagc 780 tggttctgga gaaggagcaagccctggccg acctgaactc cgtggagaag tctctggccg 840 acctcttcag aagatatgagaagatgaagg aggtcctaga aggcttccgc aagaatgaag 900 aggtgttgaa gagatgtgcgcaggagtacc tgtcccgggt gaagaaggag gagcagaggt 960 accaggccct gaaggtgcacgcggaggaga aactggacag ggccaatgct gagattgctc 1020 aggttcgagg caaggcccagcaggagcaag ccgcccacca ggccagcctg cggaaggagc 1080 agctgcgagt ggagcgccctggaaaggacg ctggagcaga agaataaaga aatagaagaa 1140 ctcaccaaga tttgtgacgaactgattgcc aaaatgggga aaagctaact ctgaaccgaa 1200 tgttttggac ttaactgttgcgtgcaatat gaccgtcggc acactgctgt tcctccagtt 1260 ccatggacag gttctgttttcacttttttg tatgcactac tgtatttcct ttctaaataa 1320 aattgatttg attgtatgcagtactaagga gactatcaga atttcttgct attggtttgc 1380 attttcctag tataattcatagcaagttga cctcagagtt cctgtatcag ggagattgtc 1440 tgattctcta ataaaagacacattgctgac cttggccttg ccctttgtac acaagttccc 1500 cagggtgagc agcttttggatttaatatga acatgtacag cgtgcatagg gactcttgcc 1560 ttaaggagtg taaacttgatctgcatttgc tgatttgttt ttaaaaaaac aagaaatgca 1620 tgtttcaaat aaaattctctattgtaaata aaattttttc tttggatctt ggcaaaaaaa 1680 aaaaaaaaaa aaaaaaaaaaaaaaaaaaaa aaaaaaattc 1720 140 774 DNA Homo sapiens SITE (697) n equalsa,t,g, or c 140 cggcacgagt tttgggatgc ctcttactct gccaagccgc ttagcgggagggaacgtgtt 60 cctgatcatc tttaccccag gcttctgtcc ggggcgtgtc aatgtagaaatcccccagcg 120 aatgttggat gaatgaatga agttgaagag agggtaggcg gggaacgaggatgaggggga 180 cggctggaga agaggtatgg gaggttcgat gtttcaggga tggcacccaaggggggacat 240 tcgaggcagc accggtagca cttcctttgc gatgaggggc gtctctttggacttcttgga 300 aaagaggtgg gcattggaaa ccagggtctg ggaacaaacc gtggtttggacataacattt 360 gttaccttca cttttctggg agttggagaa gtagaggagg aagttcagacaatttcataa 420 gtgtctaaaa agagacagtt atgcgaccat tgacgaggag taaaagtcgtctattgagca 480 tcttattcac tacaaataga agaaagaaat accagtttcc tgacaagccccaccccatgc 540 ttggccagtt cctgagtaca cttaatatat tttaggtact gtcatcaaactcaaagctcg 600 ctgtcagcct caaaggtctg aaccctagta tagattcttg tagcttgcttgaagttacag 660 tgggtcatga tcaggaattg atgctttgtt tttgttntga aacggagtntcgccantgca 720 ctccagcctg ggngacagag cccgagactc cttctcaaaa aaaaaaaaaaaaaa 774 141 1566 DNA Homo sapiens SITE (415) n equals a,t,g, or c 141ggcacgagac tatcctcaag gagcttacat atcagtaaat aaattattaa aggtggaaaa 60tgtggtaaaa gagacataat gtctcggaga gagaacaaat ttctgcttta ggagtgttct 120tagttaaggt aacattagct tctataatac gcacactccc aaatctcagt atttcaacat 180gagtttctct cttgctcatg taaagactgg tcagggaccc aggttgacag aggctcttca 240gtacatagct tccaagattg ctgtgggtgt gacatccagc cagaaatctg gtgaagagag 300agcaatgatt acacaggaac ttttaatgga ccaggcctgg gacagcgtat gtcacttcca 360ccaacatccc actcaccaga atttggtcac agggccatag ctatctgcag agaangctgg 420gaaatggaac ttagctatgt gctcaagagg aaaagtaaaa cagttattga ataattagta 480ataattagca agtaactacc taggggtcac agaggacctc tcaggtagaa tttagactta 540aagatgatgg gggagtgtgt ggaagatggg tgcagaatag ggaaaggggg gattgaagga 600agaacaagct ctagcttcac ctgcatgggt agagcccaca gtgttggtag ggacatgtta 660gctttcaaca tcagcttctt aacagtatta ttctttcatc ggaggaaatt agtctatntc 720tgaggaaaaa aaaatctgca atacgtagca atttacttac ttggatattg aatgttaaag 780cagagagaga ctttgtcctc aaaaccctcc catttcagaa gtgaggagcc tggggaggtc 840atgctctctg gatgtcacac agtgagtcac tgtcaaagcc agaatagaac ccagacctct 900cagtttccca ttccagtgct ctttctatga ggaaagtata agtttgagca tttttaaacc 960ttaattatgt agaaataacc atgatatttt atcgtaaatt atttcagtca tctcatttta 1020aattttactc caaactaaag gaaaacggta ctgatttaaa acatctatca taattcaata 1080tagcccatat ttcttcttta ggaaaaattt tttttngttt tntatcntga agacccgtgc 1140cctcttcctg tgtctcatgt agacatttca cagtccaaat atacagagca agaatagatg 1200aaatcaacat gtttaccatt attctatcta aattttcaaa gaaaaaggga acaaaaggtg 1260agtgatgact gagttgcatg gctataattg agtttttgtt gcttttattt tnataatatt 1320ttaattgaca tagatgctta aatgtatatc aaaatgcatg tcacagctct tgnacaaaga 1380taaatttgac tctagagcac attttcttta gtgagaatga taaattatct cagagcttgt 1440gattctctac ttttnnaaat cataaggtca gttctttaat taaaagataa agaaaagtag 1500gcattgtcca tgtagtgaaa tcacttttat caggataatn tagtaaccaa aaaaaaaaaa 1560aaaaaa 1566 142 1384 DNA Homo sapiens 142 tcgacccacg cgtccggccggactaaccag ctcctccagg cgctgggggc gggtgtggca 60 ggaggaagcc cgatcagccccaggctgtgg atgtgggaga agggcgagct cagggggcca 120 tcatggggtt cccccagaggcaacctggcc tatcagggct gctcctcctc gtgtgggcac 180 tggcctggcc cctgccttgtatgagcttgg agctgatccc ctacacacca cagataacag 240 cttgggacct agaagggaaggtcacagcca ccacgttctc cctggagcag cctcgctgtg 300 tcctggacgg gcttgmcggcgttgccagca ccatctggct ggtggtggcc ttcagcaacg 360 cctccagaga cttccagaacccacagacgc gagctgagat cccagccttc ccacggctgc 420 tgacggaggg gcactatatgacactgcccc tgtccctgga ccagctgccc tgtcaggacc 480 ccgcaggcgg cggcagggacgtccccttgc tgcgggtggg caatgacccc ggctgccttg 540 ctgacctcct ccagccgccctactgcaaca gccccctccc cagccccgga ccttacaggg 600 tgaagttcct cctgatggacgccaggggct caccccaggc cgagaccagg tggtccgacc 660 ccatcgctct tcaccaagggaagtcgccag cctccatcga cacgtggcca gggcgamgca 720 gtggtggtat gatcgtcatcacctctatcc tctcctccct ggccagcctc ctgctcctgg 780 ccttcctggc agcgtccaccscacgcttct ccagcctgtg gtggccggag gargccccgg 840 agcagctgag aattggctccttcatgggga agcgctacat gacccaccac atcccaccca 900 gcgaagccgc caccctgcccgtgggctgtg agcctggcyt ggaccccytc cccagcctca 960 gcccctagcc tggcccttgtggctggggcg tgtgtggctg tggccagtgt gggggcaagg 1020 acgtggtagt tattcccagcccctgcaccc tcctcctcac ccctgccama gtcccactga 1080 tgtaggacag atgtcagggttctagacgtc tttggtgcaa aaagggggtt ttattcaagc 1140 acagggacag gacccatgggcagggagagc ggcaccgggg tggtgaggag tggcccgtta 1200 tatatacttt cgagttgggagggcttagag agagcgtaag tctctaagga attttggaag 1260 caaggtctcc agggtcctgagggggctagc tgttgttagg aaaaggtcat ttattactgt 1320 ttagtaaaaa ctttcacgagaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaagggc 1380 ggcc 1384 143 537 DNAHomo sapiens SITE (429) n equals a,t,g, or c 143 gccccccaaa aagaaaggtaattaattata gttcatttcg ttttaactaa gagttactaa 60 agcatccctg gatgctgagaggtactctct aggaggcaga aacaggacca agcactgccc 120 acttatctcc acactatgctaccaattcac ctgcagtggg catgtgcttt caggagtttt 180 ttgcttggta tagacagttctatgttcgtc ttgtttcagc accctcgttt gaaggacaca 240 aagagctcta gggtcatagaaccaactctc actaactgac acagatatca ggatccaacc 300 catgcccaca gtattaccccaagtctctaa ctagctggtg taaccaataa tggaaagaaa 360 aaaagtaata ttctgttcttcaacttcaac agagaataat agtgaaagaa tggtgatatt 420 tttcctaana tggactaacaagtatcctga gttgggaggt gacttccaat agtaaacaat 480 aaaataactg agaaaatggagngaggaggg aggggagagn gagagtgggc acagaag 537 144 680 DNA Homo sapiens144 aattttttgt attttttagt agagacaggg tttcaccatg ttagccagga tggtctcgat 60ctcctgacct cgtgatccac ctgccttggg ctcccaaagt gctgggatta caggcgtgag 120cmaccacacc cggccaatca tattttttct tgttactaat tagaatcatg attctcctgg 180cattcttcat tttgttatac ctcacttcct tttccttagc aagatctttg ccatagagta 240tggaaaccag gttccttgcc agttaatctg tattgtgctt tgtcatgtat tgttactaaa 300cagctcaaga tcaaggggaa gaaatgtata tgaggctcag ttcatgttca gttttttttt 360tttcagcatt gcaacattgc cactcatcat catgagtgta gccctgtgtc aggtactgaa 420ggtaatggaa aaggtatata aggttgatcc ctgtactctt gttgggaact tgagtggtat 480gaatagagaa ggtgagttct tggggacaga ggctacagtt tagcaagctt tcctatgcgg 540accttggtaa tttctttaca ttttatagac caaagaacaa tcttaacttg cccttttttc 600taaaggcatt gtttaaaaac tgtcatcaaa tcattgcagt ttatggcaaa tggccttttt 660ttaaaaaaaa aaaaaaaaaa 680 145 1048 DNA Homo sapiens SITE (79) n equalsa,t,g, or c 145 ggcacgagag aaagtgggcc cttaccaggc accaaatctg ccagcactctgatcttggac 60 ttccagcctc ctgaactgnt gtctgcattc aaaagaacat tctattaaagctacctnaat 120 ttggcgctta tttttctnaa tcangtntct gacaatcata ttgtgtggaatggttgctgc 180 tttaagtgca ataagagcta actgccatca agagccatca gtatgttcttcaagctgcat 240 gcccagaaag ctggattggt tttcaaagaa agtgtttcta tttttctgatgacaccaaga 300 actggacatc aagtcagagg ttttgtgact cacaagatgc tgatcttgctcaggttgaaa 360 gcttccagga actggtaaga aaatagttct ggccagaatc aaagattcagccctacaagg 420 atatgttttc ctgtgaaatt atctaagaga atttcctgtt gagatataaaggcccatctg 480 atcactggat tgggctgagc agagaacaag gccaaccatg gaaatggataaatggtactg 540 aatggacaag acagttagtc atgaaagaag atggtgccaa cttgtatgttgcaaaggttt 600 cacaagttcc tcgaatgaat ccaanactgt catgggtctt actctgttacccaggctgga 660 gtgcagtart taccatcgtg gctcactgca gccttgactt ccctggctccaagtgagcct 720 cccatctcag gctcctgagt agctgggact acaggtttcc tatcctgggagcaggagagt 780 gtgcctattt gaatgacaaa ggtgccagta gtgccaggca ctacacagagaggaagtgga 840 tttgttccaa atcagatata catgtctaga tgttacagca aagccccaactaatctttag 900 aagcatattg gaactgataa ctccatttta aaatgagcaa agaatttatttcttatacca 960 acaggtatat gaaaatatgc tcaatatcac taataactgg gaaaatacaaatcaaaatca 1020 tagtaaaata aaaaaaaaaa aaaaaaaa 1048 146 930 DNA Homosapiens 146 tcgagttttt tttttttttt ttttggatat ggagtctcac tctgttgcccaggctggagt 60 gctgtggtac gatttcagct caatgcaagc tctgcctcct gggtttaagcaattctcctg 120 cctcagcctc cccagtaggt gggactacgg gtgtgcaaca caacatccggctaatttttg 180 tatttttcgt agagacaggg tttcacatgt tggccaggct ggtcttaaactcctgacctc 240 agttgatcca cctgcctggg cctcccaaag tgctgggatt acaggcaaaagccactgtgc 300 ccagctgcat tgttgctgtt ttttattgtt agttaagaga gaccaaccattagaaaaatg 360 tttaaggctt ttcaaaggaa gaatcctatg taggcagccc cactacaggttactttctga 420 tgaatgtcca ggactattac aaaatccatg attgtggaaa ttctgtcaaaagagatgaca 480 gagaaatctt gcctttggtc acaatcctgt ctgaccccaa caaaagctaaggaaatccta 540 atcaggtgtg actcatgata aagaaaaaca tgcatccaaa ttttggttcagaagtacaga 600 aagtgtgcaa cttctgtcaa gttaattaat gtatttgctc cataactccccgacatataa 660 ggtaagttgg ttggagtatg tggtttgaag gctgctttca aagatttaacgtctttgatt 720 tttttagtca ccatgggtgc caggatagaa taagatctgg agactttcgaataactgctt 780 acagatgtag ataattataa attgatacta ataaagaatg aagatctcagcattccccag 840 agagggctat ttttagaaaa aggaaatagc caaaaacaaa gtaaaacaaaaaacatcatg 900 ggatatcagg acttagctcg tgccgaattc 930 147 830 DNA Homosapiens 147 ggtcgaccca cgcgtccgct gaaaggaaaa gcactgtttg gagaatgatccacctttcaa 60 gattttactt attgttgata atgctcccac atgtcctctt ttttacgggtgatcttcatt 120 cctaatatca aagtgatatt tcttcctcca ggcaccacct ctttgatccacacaatggat 180 caaggagtta tagcagcttt taagttctac tacctgagaa gggaggacttttgcccagtc 240 ccatactgca gtggaggaag acactgagaa gactctgatg aaattctgaacagcatcaag 300 aaccttgttt aggcttggat tatgtcgcta aggactgtag gaatggcacctggaagaaga 360 cacgcaagag gtttgtcaat aacttcaaag gatttgccaa ggatgaggaagttgcaaaaa 420 tcaagaaggc tgtggttgag atggcaaaca actttaacct gggtgtggatgtggatgaca 480 ttgagtaatt cctagagggg gttcctgagg aattgactaa tgggttgctgttggaactgg 540 aataggagtg catagctgaa gaagaggtaa agaaaaagaa agtgcaggagaagggaaaaa 600 agaactccca agaatactca cagtgatggg tttagcagaa gcttcttcagactccaacaa 660 gctccttaag aagtctgaaa acatggaccc caaaactgaa aggttttcactaatagagag 720 gaaagttcat ggtgcattat ctgcctacaa gcaaaaccag gattcaaaaaaccctttgag 780 ctggagcttc aaagcacaaa aaaaaaaaaa aaaaaaaaaa aagggcggcc830 148 865 DNA Homo sapiens SITE (321) n equals a,t,g, or c 148ggtcgaccca cgcgtccgga gtagcagaaa tttgtcttct tacaagtagt ctatgagagt 60agatgctgat tttctaaatg taagggaata agaaaaactt catgattaac ttttttcacg 120tgtatttggg ctttggtggg agtaggcaag aagaatatcc gtggatttat agagtaagca 180aaagtatgtc aggaaaaact aggaagaata gggctgaact gtggcttgat ttcaggagag 240tttctgggat tcagacttga attaactgaa tgatgctgta atgtataagt gttggtatag 300gtgattttat gcaaagaaga ntaaacattg gcttactttt attatcgtat acggtatggg 360tgactactgc tgctagttca aggtctkgat tttttaaaaa tgtgtttcnt gactgtggta 420gctgggagcc ccaggataca gacttttggt taaataacat ctgctccact ctgccttccc 480gtgtgggcct ctctaaccct gggccaagca gttgagtctc tcctcggggt gcctggagtg 540agggtggata cagcttgggt aattcagcat ctgtacctaa aaacttactc aaagtaggct 600tcatgtaaag aagtcagtgg ttcttgggaa caggggtgag tgaatggagg cgaaaggtgg 660ggccctccac aggtcagtca ggccctcagg gtgggacaag agctgtaggg ctcttggtta 720taaacctgtg tggtggagac cagcaggtga gccaaactct tctttattat cagaacattt 780cactaataag ggatctcaag ggtcatctgg catcagcact ttaaccaata aaaaaaaaaa 840aaaaaaaaaa aaaaaaaggg cggcc 865 149 545 DNA Homo sapiens 149 agccagggttctagtcattt aagatgyacc tgaataaaac aaagagcctt actctcctag 60 aacttgtgtttctacctggg gagactgtca gtaaaccatc cacaaaataa atacagcaga 120 tgctgttagaagatgatggt gctatggtgt gctgtggaaa atagagaaag tagagggaag 180 tgagagggattgcgtacact aggattgtga ctttacacag aagggtcagt ggtgccattt 240 tagcaaagatctgagagagg taaaggaata agctttgcag aagtgtggga gacaaatgtt 300 ccaggtacaggaaatgacca acgccaagac cctagggtgg caatgtgtct gcttkgagtt 360 ctagagaargggtatattat acatcgcttt ttgtgactca ctttttggca aacattatgc 420 tctaaaatgaacctgtattt tggaatawat ckgtggttca ttaattctca tctttgtaca 480 gtattctattatataaatac accatgattt atttagtcaa ttaaaaaaaa aaaaaaaaaa 540 ctcga 545 15054 PRT Homo sapiens SITE (54) Xaa equals stop translation 150 Met GlnLeu Leu Cys Ser Pro Tyr Pro Glu Glu Lys Pro Lys Gly Ser 1 5 10 15 AsnArg Asn Phe Cys Asn Trp Phe Leu Ser Glu Arg Ser Ser Cys Leu 20 25 30 GlnMet Leu Leu Lys Gly His Lys Lys Leu Glu Leu Glu Lys Ile Asp 35 40 45 GluSer Ala Gly Val Xaa 50 151 46 PRT Homo sapiens SITE (46) Xaa equals stoptranslation 151 Met Ser Asn Leu Met Val Ala Met Ile Ala Val Ile Thr IleAla Val 1 5 10 15 Ser Ile Pro Ser Thr Arg Ala Asp Thr Glu Ile Ser TyrThr Tyr Trp 20 25 30 Ala Tyr Leu Ser Ile Leu Ala Gly Asn Asn Ala Trp IleXaa 35 40 45 152 25 PRT Homo sapiens SITE (25) Xaa equals stoptranslation 152 Met Ile Met Glu Glu Ile Phe Leu Asn Leu Ile Lys Asn IleTyr Lys 1 5 10 15 Ser Pro Tyr Ser Gln Cys Asn Thr Xaa 20 25 153 265 PRTHomo sapiens SITE (71) Xaa equals any of the naturally occurring L-aminoacids 153 Met Ala Thr Pro Leu Pro Pro Pro Ser Pro Arg His Leu Arg LeuLeu 1 5 10 15 Arg Leu Leu Leu Ser Gly Leu Val Leu Gly Ala Ala Leu ArgGly Ala 20 25 30 Ala Ala Gly His Pro Glu Cys Cys Arg Leu Ser Arg Glu ProGly Leu 35 40 45 Cys Pro Glu Glu Ala Gly Lys Cys Pro Pro Gly Ala His AlaCys Gly 50 55 60 Pro Ala Phe Ser Pro Ser Xaa Arg Asn Ser Lys Gly Leu PheCys Xaa 65 70 75 80 Asp Ala Pro Gly Phe Xaa Arg Gly Pro Gly Pro Thr XaaThr Xaa Asn 85 90 95 Glu Ile Asp Ser Trp Pro Lys Gly Ala Cys Pro Glu ArgAsn Leu Asp 100 105 110 Ile Asn Ser Ala Leu Thr Gln Gly Arg Thr Ala ValPro Gly Ala Cys 115 120 125 His Leu Gly Ile Xaa Gly Thr Gly Ala Gly AlaGly Ala Gly Leu Pro 130 135 140 Phe His Ser Arg Asn Pro His Ala His AlaPro His Xaa Pro Trp Val 145 150 155 160 Thr Pro Val Ser Ser Asp Pro ValHis Met Ser Pro Leu Glu Pro Arg 165 170 175 Gly Gly Gln Gly Asp Gly XaaAla Leu Val Leu Ile Leu Ala Phe Cys 180 185 190 Val Ala Gly Ala Ala AlaLeu Ser Val Ala Ser Xaa Cys Trp Cys Arg 195 200 205 Leu Gln Arg Glu IleArg Leu Thr Gln Lys Ala Glu Tyr Ala Thr Ala 210 215 220 Lys Ala Leu AlaThr Pro Ala Ala Thr Pro Asp Leu Ala Trp Gly Pro 225 230 235 240 Ala ProGly Thr Glu Arg Gly Asp Val Pro Leu Pro Ala Pro Thr Ala 245 250 255 ThrAsp Val Val Pro Gly Ala Ala Xaa 260 265 154 237 PRT Homo sapiens SITE(137) Xaa equals any of the naturally occurring L-amino acids 154 MetLys Gly Ile Leu Val Ala Gly Ile Thr Ala Val Leu Val Ala Ala 1 5 10 15Val Glu Ser Leu Ser Cys Val Gln Cys Asn Ser Trp Glu Lys Ser Cys 20 25 30Val Asn Ser Ile Ala Ser Glu Cys Pro Ser His Ala Asn Thr Ser Cys 35 40 45Ile Ser Ser Ser Ala Ser Ser Ser Leu Glu Thr Pro Val Arg Leu Tyr 50 55 60Gln Asn Met Phe Cys Ser Ala Glu Asn Cys Ser Glu Glu Thr His Ile 65 70 7580 Thr Ala Phe Thr Val His Val Ser Ala Glu Glu His Phe His Phe Val 85 9095 Ser Gln Cys Cys Gln Gly Lys Glu Cys Ser Asn Thr Ser Asp Ala Leu 100105 110 Asp Pro Pro Leu Lys Asn Val Ser Ser Asn Ala Glu Cys Pro Ala Cys115 120 125 Tyr Glu Ser Asn Gly Thr Ser Cys Xaa Gly Lys Pro Trp Lys CysTyr 130 135 140 Glu Glu Glu Gln Cys Val Xaa Leu Val Ala Glu Leu Lys AsnAsp Ile 145 150 155 160 Glu Ser Lys Ser Leu Val Leu Lys Gly Cys Ser AsnVal Ser Asn Ala 165 170 175 Thr Cys Gln Phe Leu Ser Gly Glu Asn Lys ThrLeu Gly Gly Val Ile 180 185 190 Phe Arg Lys Phe Glu Cys Ala Asn Val AsnSer Leu Thr Pro Thr Ser 195 200 205 Ala Pro Thr Thr Ser His Asn Val GlySer Lys Ala Ser Leu Tyr Leu 210 215 220 Leu Ala Leu Ala Ser Leu Leu LeuArg Gly Leu Leu Pro 225 230 235 155 314 PRT Homo sapiens SITE (49) Xaaequals any of the naturally occurring L-amino acids 155 Met Asn Gln LeuSer Phe Leu Leu Phe Leu Ile Ala Thr Thr Arg Gly 1 5 10 15 Trp Ser ThrAsp Glu Ala Asn Thr Tyr Phe Lys Glu Trp Thr Cys Ser 20 25 30 Ser Ser ProSer Leu Pro Arg Ser Cys Lys Glu Ile Lys Asp Glu Cys 35 40 45 Xaa Ser AlaPhe Asp Gly Leu Tyr Phe Leu Arg Thr Glu Asn Gly Val 50 55 60 Ile Tyr GlnThr Phe Cys Asp Met Thr Ser Gly Gly Gly Gly Trp Thr 65 70 75 80 Leu ValAla Ser Val His Glu Asn Asp Met Arg Gly Lys Cys Thr Val 85 90 95 Gly AspArg Trp Ser Ser Gln Gln Gly Ser Lys Ala Asp Tyr Pro Glu 100 105 110 GlyAsp Gly Asn Trp Ala Asn Tyr Asn Thr Phe Gly Ser Ala Glu Ala 115 120 125Ala Thr Ser Asp Asp Tyr Lys Asn Pro Gly Tyr Tyr Asp Ile Gln Ala 130 135140 Lys Asp Leu Gly Ile Trp His Val Pro Asn Lys Ser Pro Met Gln His 145150 155 160 Trp Arg Asn Ser Ser Leu Xaa Arg Tyr Arg Thr Asp Thr Gly PheLeu 165 170 175 Gln Thr Leu Gly His Asn Leu Phe Gly Ile Tyr Gln Lys TyrPro Val 180 185 190 Lys Tyr Gly Glu Gly Lys Cys Trp Thr Asp Asn Gly ProVal Ile Pro 195 200 205 Val Val Tyr Asp Phe Gly Asp Ala Gln Lys Thr AlaSer Tyr Tyr Ser 210 215 220 Pro Tyr Gly Gln Arg Glu Phe Thr Ala Gly PheVal Gln Phe Arg Val 225 230 235 240 Phe Asn Asn Glu Arg Ala Ala Asn AlaLeu Cys Ala Gly Met Arg Val 245 250 255 Thr Gly Cys Asn Thr Glu His HisCys Ile Gly Gly Gly Gly Tyr Phe 260 265 270 Pro Glu Ala Ser Pro Gln GlnCys Gly Asp Phe Ser Gly Phe Asp Trp 275 280 285 Ser Gly Tyr Gly Thr HisVal Gly Tyr Ser Ser Ser Arg Glu Ile Thr 290 295 300 Glu Ala Ala Val LeuLeu Phe Tyr Arg Xaa 305 310 156 99 PRT Homo sapiens SITE (17) Xaa equalsany of the naturally occurring L-amino acids 156 Met Leu Ala Phe Pro ValLeu Leu Glu Val Ser Trp Ser Val Leu Phe 1 5 10 15 Xaa Phe Ser Phe PheSer Pro Xaa Pro Ser Ala Pro Gln Pro Pro Thr 20 25 30 Pro Ser Arg Ser ValLeu His Ala Arg Cys Ser Asn Val Arg Ser Glu 35 40 45 Met Ala Gly Thr ArgGlu Lys Leu Leu Val Ser Phe Val Ser Gly Ser 50 55 60 Gly Met Ala Leu SerSer Leu Ala Ser Leu Phe Val Leu Phe Glu Leu 65 70 75 80 Cys Arg Ser LeuPhe Ser Gln Ala Glu Leu Pro Thr Arg Ser Ile Leu 85 90 95 Asp Gln Xaa 15737 PRT Homo sapiens SITE (8) Xaa equals any of the naturally occurringL-amino acids 157 Met Asn Pro Phe Ser Val Phe Xaa Ser Leu Cys Leu LysGln Phe Glu 1 5 10 15 Asp Val Xaa Leu Phe Leu Gly Leu Met Phe Gly XaaSer Leu Asn Gly 20 25 30 Gln Glu Gly Thr Xaa 35 158 23 PRT Homo sapiensSITE (23) Xaa equals stop translation 158 Met Val Ile Phe Ile Ile LeuLeu Thr Cys Phe Gly Phe Ser Asn Gly 1 5 10 15 Ser Phe Ser Phe Ser LeuXaa 20 159 96 PRT Homo sapiens SITE (30) Xaa equals any of the naturallyoccurring L-amino acids 159 Met Cys Phe Ile Leu Val Val Cys Phe Ala SerLeu Ile Thr Glu Cys 1 5 10 15 Pro Cys His Cys Lys Cys Cys Arg Asp ValGly Arg Gly Xaa Thr Val 20 25 30 Leu Tyr Xaa Cys Ser Met Val Gln Asn LysLeu Leu Thr Gln Val Ser 35 40 45 Leu Val Arg Asn Leu Trp Ala Met Glu ValArg His Pro Ser Cys Xaa 50 55 60 Ser Ile Gly Lys Lys Cys Phe Gln Ile LeuTrp Lys Gly Gly His Gly 65 70 75 80 Ala Gly Xaa Trp Arg Val Ala Phe GluGln Ser Asp Pro Ile Ser Val 85 90 95 160 66 PRT Homo sapiens SITE (66)Xaa equals stop translation 160 Met Val Glu Asn Trp Val Leu Glu Glu SerPro Gly Arg Leu Leu Ala 1 5 10 15 Leu Phe Val Val Arg Arg Ala Leu AlaGln Gly Gln Arg Glu Glu Lys 20 25 30 Gly Gln Pro Ala Ala Val Glu Ser AlaGly Trp Leu Pro Thr Arg Phe 35 40 45 Leu Ser Ser Gln Asp Ser Leu Pro LeuSer Ser Arg Ile Ser Asn Gly 50 55 60 Leu Xaa 65 161 222 PRT Homo sapiensSITE (86) Xaa equals any of the naturally occurring L-amino acids 161Met His Phe Gln Arg Gln Lys Leu Met Ala Val Thr Glu Tyr Ile Pro 1 5 1015 Pro Lys Pro Ala Ile His Pro Ser Cys Leu Pro Ser Pro Pro Ser Pro 20 2530 Pro Gln Glu Glu Ile Gly Leu Ile Arg Leu Leu Arg Arg Glu Ile Ala 35 4045 Ala Val Phe Gln Asp Asn Arg Met Ile Ala Val Cys Gln Asn Val Ala 50 5560 Leu Ser Ala Glu Asp Lys Leu Leu Met Arg His Gln Leu Arg Lys His 65 7075 80 Lys Ile Leu Met Lys Xaa Phe Pro Asn Gln Val Leu Lys Pro Phe Leu 8590 95 Glu Asp Ser Lys Tyr Gln Asn Leu Leu Pro Leu Phe Val Gly His Asn100 105 110 Met Leu Leu Val Ser Glu Glu Pro Lys Val Lys Glu Met Val ArgIle 115 120 125 Leu Arg Thr Val Pro Phe Leu Pro Leu Leu Gly Gly Cys IleAsp Asp 130 135 140 Thr Ile Leu Ser Arg Gln Gly Phe Ile Asn Tyr Ser LysLeu Pro Ser 145 150 155 160 Leu Pro Leu Val Gln Gly Glu Leu Val Gly GlyLeu Thr Cys Leu Thr 165 170 175 Ala Gln Thr His Ser Leu Leu Gln His GlnPro Leu Gln Leu Thr Thr 180 185 190 Leu Leu Asp Gln Tyr Ile Arg Glu GlnArg Glu Lys Asp Ser Val Met 195 200 205 Ser Ala Asn Gly Lys Pro Asp ProAsp Thr Val Pro Asp Ser 210 215 220 162 91 PRT Homo sapiens SITE (53)Xaa equals any of the naturally occurring L-amino acids 162 Met Val ValAsp Gln Lys Glu Asp Leu Ile Thr Gly Leu Gly Ile Lys 1 5 10 15 Met ValArg Lys Trp Leu Gln Gly Ser Gln Ala Trp Pro Leu Glu Arg 20 25 30 Glu GluArg Glu Gly Leu Gly Ser Leu Cys Thr Cys Cys Pro Trp Gly 35 40 45 Leu ValArg Phe Xaa Glu Ser Leu Thr His Phe Thr Gly Glu Ala Ile 50 55 60 Glu ProLeu Arg Ala Glu Val Thr Asp Pro Lys His Pro Cys Ser Cys 65 70 75 80 ValAla Glu Pro Glu Val Lys Ser Arg Ser Leu 85 90 163 74 PRT Homo sapiensSITE (51) Xaa equals any of the naturally occurring L-amino acids 163Met Glu Asn Asp Trp Gly Phe Gln Thr Thr Phe Phe Ser Leu Gly Leu 1 5 1015 Tyr Leu Phe Thr Ile Trp Trp Ser Thr Val Gly Leu Pro Trp Thr Ser 20 2530 Ser Thr Gln Arg Glu Leu Asp Met Lys Leu Glu Ala Ala Ala Leu Glu 35 4045 Gly Lys Xaa Gly Ser Leu Gly Gln Pro Arg Pro Trp Gln Glu Glu Ser 50 5560 Leu Pro Leu Gly Val Leu Asp Gly His Val 65 70 164 78 PRT Homo sapiensSITE (69) Xaa equals any of the naturally occurring L-amino acids 164Met Thr Gly Gln Ile Pro Arg Leu Ser Lys Val Asn Leu Phe Thr Leu 1 5 1015 Leu Ser Leu Trp Met Glu Leu Phe Pro Ala Glu Ala Gln Arg Gln Lys 20 2530 Ser Gln Lys Asn Glu Glu Gly Lys His Gly Pro Leu Gly Asp Asn Glu 35 4045 Glu Arg Thr Arg Val Ser Thr Asp Lys Arg Gln Asp Tyr Trp Glu Gln 50 5560 Leu Arg Cys Leu Xaa Glu Arg Phe Thr Ile Thr Ala Gly Xaa 65 70 75 16538 PRT Homo sapiens SITE (38) Xaa equals stop translation 165 Met AlaPhe Leu Leu Thr Leu Val Pro Leu Leu Pro Ser Arg Cys Leu 1 5 10 15 GlyLeu Glu Glu Met Ala Val Pro Asn Ser Thr Cys Ile Ser Pro Phe 20 25 30 SerCys Cys Tyr Gly Xaa 35 166 45 PRT Homo sapiens SITE (45) Xaa equals stoptranslation 166 Met Phe His Val Phe Val Leu Leu Leu Thr Phe Ile Ala LeuSer Pro 1 5 10 15 Ser Gly Ile Arg Leu Leu Phe Gly Phe Ile Gln Lys GlyLeu Asn Leu 20 25 30 Asn Ser Phe Met Phe Arg Leu Glu Leu Leu His Phe Xaa35 40 45 167 39 PRT Homo sapiens SITE (39) Xaa equals stop translation167 Met Thr Ser Leu Pro Ile Leu Ala Phe Gly Ala Val Tyr Trp Pro Asp 1 510 15 Leu Ala Ser His Ser Phe Ser Pro Ser Arg Ser Leu Ala Gln Thr Pro 2025 30 His Met Ser Val Ser Gly Xaa 35 168 174 PRT Homo sapiens SITE (83)Xaa equals any of the naturally occurring L-amino acids 168 Met Gln LeuIle Pro Leu Glu Gln Leu Cys Met Leu Leu Leu Met Ser 1 5 10 15 Asp AsnVal Asp Arg Cys Phe Glu Thr Cys Pro Pro Arg Thr Phe Leu 20 25 30 Pro AlaLeu Cys Lys Ile Phe Leu Asp Glu Ser Ala Pro Asp Asn Val 35 40 45 Leu GluVal Thr Ala Arg Ala Ile Thr Tyr Tyr Leu Asp Val Ser Ala 50 55 60 Glu CysThr Arg Arg Ile Val Gly Val Asp Gly Ala Ile Lys Ala Leu 65 70 75 80 CysAsn Xaa Leu Val Val Val Glu Leu Asn Asn Arg Thr Ser Arg Asp 85 90 95 LeuAla Glu Gln Cys Val Lys Val Leu Glu Leu Ile Cys Xaa Pro Glu 100 105 110Ser Gly Xaa Val Phe Xaa Ala Gly Gly Leu Asn Arg Val Ala Tyr Leu 115 120125 Pro Ser Val Asn Ser Gly His Leu Val His Lys Asp Thr Leu His Ser 130135 140 Ala Met Ala Val Val Ser Arg Leu Cys Gly Lys Met Glu Pro Gln Asp145 150 155 160 Ser Ser Leu Glu Ile Cys Val Xaa Ser Leu Ser Ser Leu Xaa165 170 169 55 PRT Homo sapiens SITE (55) Xaa equals stop translation169 Met Phe Glu Asp Thr Leu Arg Thr Leu Tyr Ile Leu Leu Phe Tyr Leu 1 510 15 Arg Tyr Ile Cys Leu Leu Ser Pro His Ile Ala Leu Met Thr Leu Ile 2025 30 Leu Ile Asp Gly Phe Leu Gln Cys Tyr Tyr Cys Ala Leu His Val Pro 3540 45 Cys Ile Ile Ala Phe Leu Xaa 50 55 170 344 PRT Homo sapiens SITE(126) Xaa equals any of the naturally occurring L-amino acids 170 MetGlu Lys Ile Gly Ser Ser Leu Pro Gln Asp Asp Asp Ala Pro Lys 1 5 10 15Lys Gln Ala Leu Tyr Leu Met Phe Asp Thr Ser Gln Glu Ser Pro Val 20 25 30Lys Ser Ser Pro Val Arg Met Ser Glu Ser Pro Thr Pro Cys Ser Gly 35 40 45Ser Ser Phe Glu Glu Thr Glu Ala Leu Val Asn Thr Ala Ala Lys Asn 50 55 60Gln His Pro Val Pro Arg Gly Leu Ala Pro Asn Gln Glu Ser His Leu 65 70 7580 Gln Val Pro Glu Lys Ser Ser Gln Lys Glu Leu Glu Ala Met Gly Leu 85 9095 Gly Thr Pro Ser Glu Ala Ile Glu Ile Arg Glu Ala Ala His Pro Thr 100105 110 Asp Val Ser Ile Ser Lys Thr Ala Leu Tyr Ser Arg Ile Xaa Thr Xaa115 120 125 Glu Val Glu Lys Pro Ala Gly Leu Leu Phe Gln Gln Pro Asp LeuAsp 130 135 140 Ser Ala Leu Gln Ile Ala Arg Ala Glu Ile Ile Thr Lys GluArg Glu 145 150 155 160 Val Ser Glu Trp Lys Asp Lys Tyr Glu Glu Ser ArgArg Glu Val Met 165 170 175 Glu Met Arg Lys Ile Val Ala Glu Tyr Glu LysThr Ile Ala Gln Met 180 185 190 Ile Glu Asp Glu Gln Arg Glu Lys Ser ValSer His Gln Thr Val Gln 195 200 205 Gln Leu Val Leu Glu Lys Glu Gln AlaLeu Ala Asp Leu Asn Ser Val 210 215 220 Glu Lys Ser Leu Ala Asp Leu PheArg Arg Tyr Glu Lys Met Lys Glu 225 230 235 240 Val Leu Glu Gly Phe ArgLys Asn Glu Glu Val Leu Lys Arg Cys Ala 245 250 255 Gln Glu Tyr Leu SerArg Val Lys Lys Glu Glu Gln Arg Tyr Gln Ala 260 265 270 Leu Lys Val HisAla Glu Glu Lys Leu Asp Arg Ala Asn Ala Glu Ile 275 280 285 Ala Gln ValArg Gly Lys Ala Gln Gln Glu Gln Ala Ala His Gln Ala 290 295 300 Ser LeuArg Lys Glu Gln Leu Arg Val Asp Ala Leu Glu Arg Thr Leu 305 310 315 320Glu Gln Lys Asn Lys Glu Ile Glu Glu Leu Thr Lys Ile Cys Asp Glu 325 330335 Leu Ile Ala Lys Met Gly Lys Ser 340 171 90 PRT Homo sapiens SITE(90) Xaa equals stop translation 171 Met Tyr His Tyr Ala Trp Leu Ile PheVal Phe Leu Val Glu Met Gly 1 5 10 15 Phe Cys His Val Gly Gln Ala GlyLeu Lys Leu Leu Thr Ser Ser Asp 20 25 30 Pro Pro Ala Ser Ala Ser Gln SerAla Gly Ile Thr Gly Val Ser His 35 40 45 His Ala Trp Gly Lys Arg Tyr PheGln Asn Ile Val Asn Asn Phe Ser 50 55 60 Pro Lys Pro Arg Gln Gly Leu IleLeu Leu Pro Arg Leu Glu Trp Gln 65 70 75 80 Gly His His Arg Ser Ser LeuGln Pro Xaa 85 90 172 104 PRT Homo sapiens 172 Met Leu Cys Pro Asn HisGly Leu Phe Pro Asp Pro Gly Phe Gln Cys 1 5 10 15 Pro Pro Leu Phe GlnGlu Val Gln Arg Asp Ala Pro His Arg Lys Gly 20 25 30 Ser Ala Thr Val LeuPro Arg Cys Pro Pro Trp Val Pro Ser Leu Lys 35 40 45 His Arg Thr Ser HisThr Ser Ser Pro Ala Val Pro Leu Ile Leu Val 50 55 60 Pro Arg Leu Pro SerLeu Gln Leu His Ser Phe Ile Gln His Ser Leu 65 70 75 80 Gly Asp Phe TyrIle Asp Thr Pro Arg Thr Glu Ala Trp Gly Lys Asp 85 90 95 Asp Gln Glu HisVal Pro Ser Arg 100 173 42 PRT Homo sapiens SITE (42) Xaa equals stoptranslation 173 Met Ser Val Leu Phe Val Ala Val Ser Leu Leu Ser Ser IleVal Pro 1 5 10 15 Asp Ile Gln Tyr Arg Leu Lys Thr Tyr Leu His Ile AspLeu Trp Lys 20 25 30 Thr Asp Thr Gln Val Leu Lys Asn Lys Xaa 35 40 17447 PRT Homo sapiens SITE (47) Xaa equals stop translation 174 Met MetLeu Gly Leu Phe Ser Pro Leu Cys Leu Val Thr Gly Ile Ala 1 5 10 15 GluGly Arg Ala Glu Asp Ala Ser Leu His Asp Ile Cys Thr Thr Gln 20 25 30 HisThr Leu Thr Phe Thr Pro Ser Tyr Pro Val Gly Gly Ser Xaa 35 40 45 175 73PRT Homo sapiens SITE (44) Xaa equals any of the naturally occurringL-amino acids 175 Met Ser Phe Ser Leu Ala His Val Lys Thr Gly Gln GlyPro Arg Leu 1 5 10 15 Thr Glu Ala Leu Gln Tyr Ile Ala Ser Lys Ile AlaVal Gly Val Thr 20 25 30 Ser Ser Gln Lys Ser Gly Glu Glu Arg Ala Met XaaThr Gln Glu Leu 35 40 45 Leu Met Asp Gln Ala Trp Asp Ser Val Cys His PheHis Gln His Pro 50 55 60 Thr His Gln Asn Xaa Val Thr Gly Pro 65 70 17629 PRT Homo sapiens SITE (29) Xaa equals stop translation 176 Met LeuSer Leu Asp Phe Pro Leu Ile Leu Leu Gly Leu Asn Leu His 1 5 10 15 IleAla Leu Leu Ser Leu Leu Val Pro Arg Leu Ser Xaa 20 25 177 67 PRT Homosapiens 177 Met Ile Phe Arg Asn Gly Val Arg Leu Val Phe Val Phe Val LeuPhe 1 5 10 15 Tyr Thr Ser Thr Gln Ser Leu Phe Asn Ser Leu Gln Thr AlaGlu Tyr 20 25 30 Val Leu Phe Cys Gln Gln Arg Leu Ser Leu Tyr Glu Pro SerHis Val 35 40 45 Leu Cys Leu Cys Met Ser Pro His Arg Lys His Thr Arg GluSer Asp 50 55 60 Thr Ser Gly 65 178 24 PRT Homo sapiens SITE (24) Xaaequals stop translation 178 Met Asn Phe Leu Leu Leu Ile Phe Pro Tyr PheSer Ser Leu Leu Gly 1 5 10 15 Glu Val Glu Val Val Lys Cys Xaa 20 179 31PRT Homo sapiens SITE (31) Xaa equals stop translation 179 Met Ser ProGly Arg Val Ser Val Val Ser Leu Gln Gly Ser Gln Leu 1 5 10 15 Cys LeuLeu Val Ser Ile Ala Ile Met Gly Leu Leu Leu Phe Xaa 20 25 30 180 11 PRTHomo sapiens SITE (11) Xaa equals stop translation 180 Met Ala Tyr AlaPhe His Arg Thr Ser Thr Xaa 1 5 10 181 32 PRT Homo sapiens SITE (32) Xaaequals stop translation 181 Met Ser Val Lys Val Gly Ser Leu Leu Val LeuVal Tyr Phe Thr Leu 1 5 10 15 Gly Pro Val Val Ala Glu Leu Glu Val ThrLeu Pro Ser His Ser Xaa 20 25 30 182 36 PRT Homo sapiens SITE (36) Xaaequals stop translation 182 Met Ile Val Ile Thr Ser Ile Leu Ser Ser LeuAla Ser Leu Leu Leu 1 5 10 15 Leu Ala Phe Leu Ala Ala Ser Thr Ala ArgLeu Ser Pro Gln Ser Leu 20 25 30 Pro Glu Thr Xaa 35 183 35 PRT Homosapiens SITE (35) Xaa equals stop translation 183 Met Ser Gly Leu GluSer Ala Arg Val Leu Leu Cys Ala Leu Gly Ser 1 5 10 15 Phe Leu Leu AsnSer Leu Leu Ser Thr Phe Arg Leu Asn Ser Ser Ala 20 25 30 Pro Ser Xaa 35184 29 PRT Homo sapiens SITE (29) Xaa equals stop translation 184 MetHis Ser Ile Ile Val Lys Glu Leu Ile Val Thr Phe Phe Leu Gly 1 5 10 15Ile Thr Val Leu Leu Leu Leu Met Gln Arg Ser Leu Xaa 20 25 185 6 PRT Homosapiens SITE (6) Xaa equals stop translation 185 Met Gly Tyr Leu Asn Xaa1 5 186 58 PRT Homo sapiens 186 Met Pro Phe Ala Trp Asn Asp Leu Thr SerLeu Leu Phe Tyr Leu Ala 1 5 10 15 Gly Cys Phe Ser Ser Cys Arg Leu GlyGln Gly Thr Pro Gly Ser Leu 20 25 30 Pro Trp Thr Ser Asn Glu Glu Gly IleIle Gln Gly Pro Thr Pro Met 35 40 45 Phe Trp Asn Leu Thr Pro Phe Ser GlyThr 50 55 187 406 PRT Homo sapiens SITE (273) Xaa equals any of thenaturally occurring L-amino acids 187 Met Leu Leu Leu Trp Val Ser ValVal Ala Ala Leu Ala Leu Ala Val 1 5 10 15 Leu Ala Pro Gly Ala Gly GluGln Arg Arg Arg Ala Ala Lys Ala Pro 20 25 30 Asn Val Val Leu Val Val SerAsp Ser Tyr Asp Gly Arg Leu Thr Phe 35 40 45 His Pro Gly Ser Gln Val ValLys Leu Pro Phe Ile Asn Phe Met Lys 50 55 60 Thr Arg Gly Thr Ser Phe LeuAsn Ala Tyr Thr Asn Ser Pro Ile Cys 65 70 75 80 Cys Pro Ser Arg Ala AlaMet Trp Ser Gly Leu Phe Thr His Leu Thr 85 90 95 Glu Ser Trp Asn Asn PheLys Gly Leu Asp Pro Asn Tyr Thr Thr Trp 100 105 110 Met Asp Val Met GluArg His Gly Tyr Arg Thr Gln Lys Phe Gly Lys 115 120 125 Leu Asp Tyr ThrSer Gly His His Ser Ile Ser Asn Arg Val Glu Ala 130 135 140 Trp Thr ArgAsp Val Ala Phe Leu Leu Arg Gln Glu Gly Arg Pro Met 145 150 155 160 ValAsn Leu Ile Arg Asn Arg Thr Lys Val Arg Val Met Glu Arg Asp 165 170 175Trp Gln Asn Thr Asp Lys Ala Val Asn Trp Leu Arg Lys Glu Ala Ile 180 185190 Asn Tyr Thr Glu Pro Phe Val Ile Tyr Leu Gly Leu Asn Leu Pro His 195200 205 Pro Tyr Pro Ser Pro Ser Ser Gly Glu Asn Phe Gly Ser Ser Thr Phe210 215 220 His Thr Ser Leu Tyr Trp Leu Glu Lys Val Ser His Asp Ala IleLys 225 230 235 240 Ile Pro Lys Trp Ser Pro Leu Ser Glu Met His Pro ValAsp Tyr Tyr 245 250 255 Ser Ser Tyr Thr Lys Asn Cys Thr Gly Arg Phe ThrLys Lys Glu Ile 260 265 270 Xaa Asn Ile Arg Ala Phe Tyr Tyr Ala Met CysAla Glu Thr Asp Ala 275 280 285 Met Leu Gly Glu Ile Ile Leu Ala Leu HisGln Leu Asp Leu Leu Gln 290 295 300 Lys Thr Ile Val Ile Tyr Ser Ser AspHis Gly Glu Leu Ala Met Glu 305 310 315 320 His Arg Gln Phe Tyr Lys MetSer Met Tyr Glu Ala Ser Ala His Val 325 330 335 Pro Leu Leu Met Met GlyPro Gly Ile Lys Ala Gly Leu Gln Val Ser 340 345 350 Asn Val Val Ser LeuVal Asp Ile Tyr Pro Thr Met Leu Asp Ile Ala 355 360 365 Gly Ile Pro LeuPro Gln Asn Leu Ser Gly Tyr Ser Ser Leu Pro Leu 370 375 380 Ser Ser GluThr Phe Lys Asn Glu His Lys Val Lys Asn Leu His Pro 385 390 395 400 ProTrp Ile Thr Glu Xaa 405 188 37 PRT Homo sapiens SITE (37) Xaa equalsstop translation 188 Met Asn Gly Leu Val Arg Pro Val Glu Leu Asn Ser LeuLeu Leu Pro 1 5 10 15 Val Val Arg Tyr Gln Val Ala Gln Pro Gln Lys LeuLeu Asn Val Phe 20 25 30 Val Gly Gly Leu Xaa 35 189 57 PRT Homo sapiensSITE (51) Xaa equals any of the naturally occurring L-amino acids 189Met Lys Ala Leu Val Gly Asn Ser Pro Pro Val Gly Asp Ser Gly Thr 1 5 1015 Gln Pro Pro Ser Ala Leu Arg Leu Cys Leu Leu Lys Val Leu Arg Val 20 2530 Leu Ser Met Tyr Leu Ala Asn Gly Glu Arg Val Trp Arg Thr His Lys 35 4045 Arg Val Xaa His His Val Leu Arg Gly 50 55 190 128 PRT Homo sapiensSITE (127) Xaa equals any of the naturally occurring L-amino acids 190Met Phe Val Leu Leu Tyr Val Thr Ser Phe Ala Ile Cys Ala Ser Gly 1 5 1015 Gln Pro Arg Gly Asn Gln Leu Lys Gly Glu Asn Tyr Ser Pro Arg Tyr 20 2530 Ile Cys Ser Ile Pro Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Ala 35 4045 Asn Gly Ser Pro Gly Pro His Gly Arg Ile Gly Leu Pro Gly Arg Asp 50 5560 Gly Arg Asp Gly Arg Lys Gly Glu Lys Gly Glu Lys Gly Thr Ala Gly 65 7075 80 Leu Arg Gly Lys Thr Gly Pro Leu Gly Leu Ala Gly Glu Lys Gly Asp 8590 95 Gln Gly Glu Thr Gly Lys Lys Gly Pro Ile Gly Pro Glu Gly Glu Lys100 105 110 Gly Glu Val Gly Pro Ile Gly Pro Pro Gly Pro Lys Gly Asp XaaXaa 115 120 125 191 21 PRT Homo sapiens SITE (21) Xaa equals stoptranslation 191 Met Lys Phe Ile Met Leu Leu Leu Leu Pro Ser Ile Phe ProThr Thr 1 5 10 15 Val Glu Met Ile Xaa 20 192 143 PRT Homo sapiens SITE(92) Xaa equals any of the naturally occurring L-amino acids 192 Met CysAla Phe Pro Trp Leu Leu Leu Leu Leu Leu Leu Gln Glu Gly 1 5 10 15 SerGln Arg Arg Leu Trp Arg Trp Cys Gly Ser Glu Glu Val Val Ala 20 25 30 ValLeu Gln Glu Ser Ile Ser Leu Pro Leu Glu Ile Pro Pro Asp Glu 35 40 45 GluVal Glu Asn Ile Ile Trp Ser Ser His Lys Ser Leu Ala Thr Val 50 55 60 ValPro Gly Lys Glu Gly His Pro Ala Thr Ile Met Val Thr Asn Pro 65 70 75 80His Tyr Gln Gly Gln Val Ser Phe Leu Asp Pro Xaa Tyr Ser Leu His 85 90 95Ile Ser Asn Leu Ser Trp Glu Asp Ser Gly Leu Tyr Gln Ala Gln Val 100 105110 Asn Leu Arg Thr Ser Gln Ile Ser Thr Met Gln Gln Tyr Asn Leu Cys 115120 125 Val Tyr Arg Trp Leu Ser Glu Xaa Pro Xaa His Cys Glu Leu Xaa 130135 140 193 110 PRT Homo sapiens SITE (110) Xaa equals stop translation193 Met Ile Lys Lys Asp Lys Tyr His Lys Lys Val Phe Leu Phe Gly Trp 1 510 15 Phe Phe Cys Leu Phe Val Phe Phe Leu Arg Leu Ser Leu Ser Leu Leu 2025 30 Pro Lys Leu Glu Cys Asn Leu Gly Ser Leu Gln Pro Pro Pro Pro Arg 3540 45 Phe Gln Arg Phe Ser Cys Leu Ser Leu Leu Asn Ser Trp Asp Tyr Arg 5055 60 Arg Pro Pro Pro His Leu Ala Asn Phe Cys Val Val Ser Arg Gly Gly 6570 75 80 Val Ser Ser Cys Trp Pro Gly Trp Ser Arg Thr Pro Asp Leu Met Ile85 90 95 Arg Leu Pro Arg Pro Pro Arg Val Leu Gly Leu Gln Ala Xaa 100 105110 194 80 PRT Homo sapiens SITE (73) Xaa equals any of the naturallyoccurring L-amino acids 194 Met Phe Leu Thr Ile Ile Val Cys Gly Met ValAla Ala Leu Ser Ala 1 5 10 15 Ile Arg Ala Asn Cys His Gln Glu Pro SerVal Cys Leu Gln Ala Ala 20 25 30 Cys Pro Glu Ser Trp Ile Gly Phe Gln ArgLys Cys Phe Tyr Phe Ser 35 40 45 Asp Asp Thr Lys Asn Trp Thr Ser Ser GlnArg Phe Cys Asp Ser Gln 50 55 60 Asp Ala Asp Leu Ala Gln Val Glu Xaa PheGln Glu Leu Xaa Arg Lys 65 70 75 80 195 210 PRT Homo sapiens SITE (210)Xaa equals stop translation 195 Met Cys Pro Leu Trp Arg Leu Leu Ile PheLeu Gly Leu Leu Ala Leu 1 5 10 15 Pro Leu Ala Pro His Lys Gln Pro TrpPro Gly Leu Ala Gln Ala His 20 25 30 Arg Asp Asn Lys Ser Thr Leu Ala ArgIle Ile Ala Gln Gly Leu Ile 35 40 45 Lys His Asn Ala Glu Ser Arg Ile GlnAsn Ile His Phe Gly Asp Arg 50 55 60 Leu Asn Ala Ser Ala Gln Val Ala ProGly Leu Val Gly Trp Leu Ile 65 70 75 80 Ser Gly Arg Lys His Gln Gln GlnGln Glu Ser Ser Ile Asn Ile Thr 85 90 95 Asn Ile Gln Leu Asp Cys Gly GlyIle Gln Ile Ser Phe His Lys Glu 100 105 110 Trp Phe Ser Ala Asn Ile SerLeu Glu Phe Asp Leu Glu Leu Arg Pro 115 120 125 Ser Phe Asp Asn Asn IleIle Lys Met Cys Ala His Met Ser Ile Val 130 135 140 Val Glu Phe Trp LeuGlu Lys Asp Glu Phe Gly Arg Arg Asp Leu Val 145 150 155 160 Ile Gly LysCys Asp Ala Glu Pro Ser Ser Val His Val Ala Ile Leu 165 170 175 Thr GluAla Ile Pro Pro Lys Met Asn Gln Phe Leu Tyr Asn Leu Lys 180 185 190 GluAsn Leu Gln Lys Val Leu Pro His Met Val Glu Ser Gln Pro Leu 195 200 205Ala Xaa 210 196 149 PRT Homo sapiens SITE (61) Xaa equals any of thenaturally occurring L-amino acids 196 Met Arg Lys Ile Ala Gln Cys AlaPro Gly Val Val Glu Leu Val Leu 1 5 10 15 Ile Pro Leu Arg Gln Arg LeuGlu Glu Arg Gln Arg Arg Arg Lys Gln 20 25 30 Gly Ala Gly Ser Leu Gln GluLeu Ala Pro Gln Asp Gly Ser Gly Tyr 35 40 45 Met Asp Val Gly Val Ser GlnLys Ala Arg Gly Glu Xaa Val Pro Asp 50 55 60 Pro Gln Gly Gly Gly Gln LeuSer Trp Asp Arg Pro Pro Ala Pro Arg 65 70 75 80 Pro Pro Ala Tyr Asn ArgAla Leu Gln Gly Asp Pro Ser Phe Val Leu 85 90 95 Gln Ile Ala Glu Lys GluGln Glu Leu Leu Ala Ser Gln Glu Thr Val 100 105 110 Gln Val Leu Gln MetLys Val Arg Arg Leu Glu His Leu Leu Gln Leu 115 120 125 Lys Asn Val ArgIle Glu Asn Leu Ser Arg Arg Leu Gln Xaa Ala Glu 130 135 140 Arg Lys GlnArg Xaa 145 197 36 PRT Homo sapiens SITE (36) Xaa equals stoptranslation 197 Met His Ile Thr Ser Leu Val Gly Ala Gly Thr Leu Met ValLeu Leu 1 5 10 15 Leu Leu Ile Leu Leu Leu Glu Cys Phe Phe Val Ala GluAla Leu Val 20 25 30 Met Arg Ser Xaa 35 198 258 PRT Homo sapiens SITE(258) Xaa equals stop translation 198 Met Ala Ala Leu Thr Thr Val ValVal Ala Ala Ala Ala Thr Ala Val 1 5 10 15 Ala Gly Ala Val Ala Gly AlaGly Ala Ala Thr Gly Thr Gly Val Gly 20 25 30 Ala Thr Pro Ala Pro Gln GlnSer Asp Gly Cys Phe Ser Thr Ser Gly 35 40 45 Gly Ile Arg Pro Phe His LeuGln Asn Trp Lys Gln Lys Val Asn Gln 50 55 60 Thr Lys Lys Ala Glu Phe ValArg Thr Ala Glu Lys Phe Lys Asn Gln 65 70 75 80 Val Ile Asn Met Glu LysAsp Lys His Ser His Phe Tyr Asn Gln Lys 85 90 95 Ser Asp Phe Arg Phe GluHis Ser Met Leu Glu Glu Leu Glu Asn Lys 100 105 110 Leu Ile His Ser ArgLys Thr Glu Arg Ala Lys Phe Gln Gln Gln Leu 115 120 125 Ala Lys Ile HisAsn Asn Val Lys Lys Leu Gln His Gln Leu Lys Asp 130 135 140 Val Lys ProThr Pro Asp Phe Val Glu Lys Leu Arg Glu Met Met Glu 145 150 155 160 GluIle Glu Asn Ala Ile Asn Thr Phe Lys Glu Glu Gln Arg Leu Ile 165 170 175Tyr Glu Glu Leu Ile Lys Glu Glu Lys Thr Thr Asn Asn Glu Leu Ser 180 185190 Ala Ile Ser Arg Lys Ile Asp Thr Trp Ala Leu Gly Asn Ser Glu Thr 195200 205 Glu Lys Ala Phe Arg Ala Ile Ser Ser Lys Val Pro Val Asp Lys Val210 215 220 Thr Pro Ser Thr Leu Pro Glu Glu Val Leu Asp Phe Glu Lys PheLeu 225 230 235 240 Gln Gln Thr Gly Gly Arg Gln Gly Ala Trp Asp Val IleThr Arg Thr 245 250 255 Leu Xaa 199 59 PRT Homo sapiens SITE (11) Xaaequals any of the naturally occurring L-amino acids 199 Met Leu Cys LeuLeu Val Leu Thr Gly Leu Xaa Val Leu Ile Val Gly 1 5 10 15 Ile His IleLeu Glu Leu Leu Ile Asp Glu Ala Ala Met Pro Arg Gly 20 25 30 Met Gln GlyThr Ser Leu Gly Gln Val Ser Phe Ser Lys Leu Gly Ser 35 40 45 Phe Ala SerSer Ala Ser Leu Ser Ala Arg Xaa 50 55 200 34 PRT Homo sapiens SITE (34)Xaa equals stop translation 200 Met Phe Phe Val Leu Leu Cys Phe Trp LeuPhe Pro Phe Ser Lys Asn 1 5 10 15 Ser Pro Leu Trp Gly Met Leu Arg SerSer Phe Phe Ile Ser Ile Asn 20 25 30 Leu Xaa 201 26 PRT Homo sapiensSITE (26) Xaa equals stop translation 201 Met Ser Leu Ile Leu Leu LeuSer Val Thr Leu Leu His Leu Ser Phe 1 5 10 15 Ser Val Gly Phe Phe LeuPhe Arg Leu Xaa 20 25 202 34 PRT Homo sapiens SITE (34) Xaa equals stoptranslation 202 Met Lys Ser Val Ile Phe Ile Gln Ser Val Ile Leu Phe PheLeu Pro 1 5 10 15 Met Ser Gly Asp His Gln Gly Ile Ser Gly Leu Asp GluLeu Pro Gln 20 25 30 Ala Xaa 203 58 PRT Homo sapiens 203 Met Ser Ser PheLeu Arg Val Ile Phe Ile Pro Asn Ile Lys Val Ile 1 5 10 15 Phe Leu ProPro Gly Thr Thr Ser Leu Ile His Thr Met Asp Gln Gly 20 25 30 Val Ile AlaAla Phe Lys Phe Tyr Tyr Leu Arg Arg Glu Asp Phe Cys 35 40 45 Pro Val ProTyr Cys Ser Gly Gly Arg His 50 55 204 75 PRT Homo sapiens SITE (66) Xaaequals any of the naturally occurring L-amino acids 204 Met Lys Pro ThrLeu Ser Lys Phe Leu Gly Thr Asp Ala Glu Leu Pro 1 5 10 15 Lys Leu TyrPro Pro Ser Leu Gln Ala Pro Arg Gly Glu Thr Gln Leu 20 25 30 Leu Gly ProGly Leu Glu Arg Pro Thr Arg Glu Gly Arg Val Glu Gln 35 40 45 Met Leu PheAsn Gln Lys Ser Val Ser Trp Gly Ser Gln Leu Pro Gln 50 55 60 Ser Xaa AsnThr Phe Leu Lys Asn Xaa Asp Pro 65 70 75 205 66 PRT Homo sapiens SITE(63) Xaa equals any of the naturally occurring L-amino acids 205 Met ThrTrp Lys Gly Trp Ser Arg Thr Arg Ile Trp Lys Pro Ser Leu 1 5 10 15 ProGln Leu Phe Thr Met Tyr Leu Leu Ala Gln Ile Arg Ala Ala Ser 20 25 30 ArgAla Ser Glu Asp Ser Cys Ser Tyr Ser Ser Asp Thr Met Trp Pro 35 40 45 GlnSer Gly Asn Ser Ser Thr Phe Ala Phe Phe Arg Pro Arg Xaa Lys 50 55 60 MetArg 65 206 44 PRT Homo sapiens SITE (44) Xaa equals stop translation 206Met Leu Ser Phe Val Ser Arg Cys His Trp Ser Ser Ile Ala Glu Glu 1 5 1015 Ser Glu Phe Leu Phe Leu Ile Leu Val Cys Tyr Phe Ser Ser Ser Cys 20 2530 Ser Ser Cys Ile Ile His Gln Trp Tyr Tyr Val Xaa 35 40 207 32 PRT Homosapiens SITE (32) Xaa equals stop translation 207 Met Leu Gln Thr LeuIle Leu Ile Phe Leu Leu Leu Leu Pro Cys Tyr 1 5 10 15 Leu Glu Leu LeuCys Phe Ser Leu Ile Ser Ser Ser Ala Lys Thr Xaa 20 25 30 208 48 PRT Homosapiens SITE (11) Xaa equals any of the naturally occurring L-aminoacids 208 Met Thr Pro Trp Leu Leu Ile Leu Val Ser Xaa Gly Phe Leu LysSer 1 5 10 15 Ile Ser Asp Pro Gln Phe Gln Glu Leu Ser Ile Asn Ile AlaSer Cys 20 25 30 His Pro Gly Thr Val Met Pro Tyr Ser Gly Thr Ser His LeuLys Xaa 35 40 45 209 37 PRT Homo sapiens SITE (37) Xaa equals stoptranslation 209 Met Thr Gly Thr Pro Ala Trp Ala His Leu Leu Leu Leu LeuLeu Leu 1 5 10 15 Gly Ser Ala Pro Gln Thr Arg Leu Trp Pro Pro Ser GlnCys Pro Val 20 25 30 Thr Ser Pro Glu Xaa 35 210 74 PRT Homo sapiens SITE(74) Xaa equals stop translation 210 Met Gly Val Lys Leu Glu Ile Phe ArgMet Ile Ile Tyr Leu Thr Phe 1 5 10 15 Pro Val Ala Met Phe Trp Val SerAsn Gln Ala Glu Trp Phe Glu Asp 20 25 30 Asp Val Ile Gln Arg Lys Arg GluLeu Trp Pro Pro Glu Lys Leu Gln 35 40 45 Glu Ile Glu Glu Phe Lys Glu ArgLeu Arg Lys Arg Arg Glu Glu Lys 50 55 60 Leu Leu Arg Asp Ala Gln Gln AsnSer Xaa 65 70 211 41 PRT Homo sapiens SITE (41) Xaa equals stoptranslation 211 Met Pro Phe Ser Ser Ser Val Lys Cys Leu Phe Gly Val LeuLeu Arg 1 5 10 15 Phe Cys Phe Val Val Phe Ser Val Val Val Phe Thr PhePhe Leu Ser 20 25 30 Ile Pro Lys Arg Thr Leu Gly Tyr Xaa 35 40 212 54PRT Homo sapiens SITE (54) Xaa equals stop translation 212 Met Trp HisLeu Ser Phe His Cys Leu Leu Leu Leu Leu Pro Leu Cys 1 5 10 15 Glu ValThr His Ser Leu Phe Ala Phe Tyr His Asn Trp Lys Leu Phe 20 25 30 Glu AlaSer Leu Glu Thr Glu Ala Ala Met Leu Pro Val Gln Pro Ala 35 40 45 Glu ProArg Ala Asn Xaa 50 213 63 PRT Homo sapiens SITE (63) Xaa equals stoptranslation 213 Met Pro Glu Asn Leu Val Leu Ile Leu Ala Leu Leu Leu SerVal Cys 1 5 10 15 Gly Leu Lys Gln Val Ile Phe Leu Ser Ala Ser Ile TyrSer Lys Met 20 25 30 Cys Thr Leu Ile Ala Thr Lys Lys Val Val Ala Lys ThrArg Asn Asp 35 40 45 Ala Tyr Trp Tyr Leu Ile Ser Leu Lys His Ile Val GlyPhe Xaa 50 55 60 214 176 PRT Homo sapiens SITE (142) Xaa equals any ofthe naturally occurring L-amino acids 214 Met Tyr Trp Ile Val Phe AlaLeu Tyr Thr Val Ile Glu Thr Val Ala 1 5 10 15 Asp Gln Thr Val Ala TrpPhe Pro Leu Tyr Tyr Glu Leu Lys Ile Ala 20 25 30 Phe Val Ile Trp Leu LeuSer Pro Tyr Thr Lys Gly Ala Ser Leu Ile 35 40 45 Tyr Arg Lys Phe Leu HisPro Leu Leu Ser Ser Lys Glu Arg Glu Ile 50 55 60 Asp Asp Tyr Ile Val GlnAla Lys Glu Arg Gly Tyr Glu Thr Met Val 65 70 75 80 Asn Phe Gly Arg GlnGly Leu Asn Leu Ala Ala Thr Ala Ala Val Thr 85 90 95 Ala Ala Val Lys SerGln Gly Ala Ile Thr Glu Arg Leu Arg Ser Phe 100 105 110 Ser Met His AspLeu Thr Thr Ile Gln Gly Asp Glu Pro Val Gly Gln 115 120 125 Arg Pro TyrGln Pro Leu Pro Glu Ala Lys Lys Lys Ser Xaa Gln Pro 130 135 140 Pro ValAsn Gln Xaa Val Met Glu Phe His Xaa Lys Thr Xaa Met Xaa 145 150 155 160Lys Gln Xaa Lys Lys Gln Arg Gly His Ile Gln Ile Met Arg Cys Xaa 165 170175 215 40 PRT Homo sapiens SITE (40) Xaa equals stop translation 215Met Arg Glu Cys Tyr Phe Leu Gly Asn Phe Leu Leu Val Phe Leu Ile 1 5 1015 Leu Ala Ser Ser Phe Ile Tyr Val Leu Val Thr Gln Val Leu Gly Gly 20 2530 Pro Ala Thr Leu Leu Ala Phe Xaa 35 40 216 55 PRT Homo sapiens SITE(55) Xaa equals stop translation 216 Met Val Leu Gln Asn Thr Asn Thr LeuLeu Ile Val Ser Ala Phe Leu 1 5 10 15 Leu Ser Met Leu Phe Phe Lys PheSer Ile Ala Ile Phe Leu Val Thr 20 25 30 Asn Leu Ser Phe Glu Arg Ser AsnLeu Leu Leu Gly Pro Ser Ser Asp 35 40 45 Leu Phe Leu Asn Phe Lys Xaa 5055 217 47 PRT Homo sapiens SITE (47) Xaa equals stop translation 217 MetTyr Ile Phe His Phe Val Phe Leu Ile Gly Tyr Ala Met Cys Gly 1 5 10 15Ile Gln Val Thr Asn Val Thr Leu Ala Ser Gly Pro Ser Asn Leu His 20 25 30Val Tyr Leu Leu Gln Ser Tyr Leu Thr Arg Gly Pro Asn His Xaa 35 40 45 218180 PRT Homo sapiens SITE (180) Xaa equals stop translation 218 Met LeuTyr Tyr Leu Trp Met Leu His Ser Val Thr Leu Phe Leu Asn 1 5 10 15 LeuLeu Ala Cys Leu Ala Trp Phe Ser Gly Asn Ser Ser Lys Gly Val 20 25 30 AspPhe Gly Leu Ser Ile Leu Trp Phe Leu Ile Phe Thr Pro Cys Ala 35 40 45 PheLeu Cys Trp Tyr Arg Pro Ile Tyr Lys Ala Phe Arg Ser Asp Asn 50 55 60 SerPhe Ser Phe Phe Val Phe Phe Phe Val Phe Phe Cys Gln Ile Gly 65 70 75 80Ile Tyr Ile Ile Gln Leu Val Gly Ile Pro Gly Leu Gly Asp Ser Gly 85 90 95Trp Ile Ala Ala Leu Ser Thr Leu Asp Asn His Ser Leu Ala Ile Ser 100 105110 Val Ile Met Met Val Val Ala Gly Phe Phe Thr Leu Cys Ala Val Leu 115120 125 Ser Val Phe Leu Leu Gln Arg Val His Ser Leu Tyr Arg Arg Thr Gly130 135 140 Ala Ser Phe Gln Gln Ala Gln Glu Glu Phe Ser Gln Gly Ile PheSer 145 150 155 160 Ser Arg Thr Phe His Arg Ala Ala Ser Ser Ala Ala GlnGly Ala Phe 165 170 175 Gln Gly Asn Xaa 180 219 99 PRT Homo sapiens SITE(99) Xaa equals stop translation 219 Met Lys Leu Met Val Leu Val Phe ThrIle Gly Leu Thr Leu Leu Leu 1 5 10 15 Gly Val Gln Ala Met Pro Ala AsnArg Leu Ser Cys Tyr Arg Lys Ile 20 25 30 Leu Lys Asp His Asn Cys His AsnLeu Pro Glu Gly Val Ala Asp Leu 35 40 45 Thr Gln Ile Asp Val Asn Val GlnAsp His Phe Trp Asp Gly Lys Gly 50 55 60 Cys Glu Met Ile Cys Tyr Cys AsnPhe Ser Glu Leu Leu Cys Cys Pro 65 70 75 80 Lys Asp Val Phe Phe Gly ProLys Ile Ser Phe Val Ile Pro Cys Asn 85 90 95 Asn Gln Xaa 220 44 PRT Homosapiens SITE (44) Xaa equals stop translation 220 Met Gly Gly Lys GlyIle Asn Tyr Thr Met Pro His Ile Cys Leu Leu 1 5 10 15 Leu Leu Asn AlaLeu Val Val Ser Cys Leu Leu Leu Glu Ala Ile Leu 20 25 30 Leu Gln His LeuVal Leu Cys Asn Glu Leu Pro Xaa 35 40 221 42 PRT Homo sapiens SITE (42)Xaa equals stop translation 221 Met Phe Met Leu Cys Asn Leu Leu Leu ProLeu Leu Glu Phe Ile Phe 1 5 10 15 Gly Ser Thr Tyr Leu Ser Thr Asp LeuTyr Leu His Thr Cys Met Lys 20 25 30 Asn Val Phe Leu His Ile His Ser PheXaa 35 40 222 52 PRT Homo sapiens SITE (52) Xaa equals stop translation222 Met Ala Val Pro Ser Gly Cys Trp Pro Ser Trp Pro Arg Pro Ser Ser 1 510 15 Trp Trp Ser Thr Arg Ile Ser Pro Arg Ser Ala Thr Pro Leu Thr Ala 2025 30 Ser Thr Trp Ser Leu Val Thr Cys Ser Ser Gln Val Ser Ala Cys Gly 3540 45 Thr Ser Ile Xaa 50 223 32 PRT Homo sapiens SITE (32) Xaa equalsstop translation 223 Met Val Ser Leu Asn Leu Ser Leu Pro Asn Asn Ile IleSer Leu Val 1 5 10 15 Phe Phe Phe Leu Leu Gln Pro Val Gln Lys Gly ValSer Gly Gly Xaa 20 25 30 224 54 PRT Homo sapiens SITE (54) Xaa equalsstop translation 224 Met Leu Val Leu Met Thr Thr Cys Ile Leu Ala Ala ValCys Val His 1 5 10 15 Thr Ala Gln Cys Ala Pro Asp Ser Arg Met Asp AsnAsp Cys Pro Ser 20 25 30 His Gln Ala Gln Ile His Phe Arg Ala Ser Glu ValArg Arg Gly Trp 35 40 45 Thr Phe Asn His Asp Xaa 50 225 41 PRT Homosapiens SITE (41) Xaa equals stop translation 225 Met Gly Pro Ser GlnArg Glu Val Thr Val Gln Trp His Arg Ala Leu 1 5 10 15 Phe Leu Leu ProLeu Leu Leu Leu Ser Thr Arg Thr Glu Thr Lys Asn 20 25 30 Phe Gly Phe LysTrp Leu Lys Asp Xaa 35 40 226 31 PRT Homo sapiens SITE (31) Xaa equalsstop translation 226 Met Gln Leu Ser Lys Phe Leu Leu Phe Leu Phe Val TyrThr Arg Glu 1 5 10 15 Asn Pro Thr Ser Ala Cys Val Trp Gly Glu Lys SerThr Val Xaa 20 25 30 227 60 PRT Homo sapiens SITE (60) Xaa equals stoptranslation 227 Met Val Val Val Ser Thr Asn Gly Phe Leu Leu Leu Leu LeuPhe Leu 1 5 10 15 Asn Arg Lys Ser Gly Leu Cys Ser Tyr Arg Lys Ala ValHis Arg Leu 20 25 30 Ser Ser Cys Pro Ser Arg His Gln Ala Gly Pro Arg IleLys Cys Asp 35 40 45 Phe Lys Trp Gly Lys Leu Cys Tyr Ser Cys Ala Xaa 5055 60 228 35 PRT Homo sapiens SITE (35) Xaa equals stop translation 228Met Gly Trp Gly Lys Glu Val Val Ser Leu Ile Val Leu Leu Val Asn 1 5 1015 Leu Phe Leu Cys Pro Trp Ala Leu Gly Leu Cys Leu Leu Ser Val Ser 20 2530 Ser Leu Xaa 35 229 39 PRT Homo sapiens SITE (39) Xaa equals stoptranslation 229 Met Met Asn Ile Leu Leu Leu Lys Tyr Ile Leu Glu Ile LeuIle Leu 1 5 10 15 Ser Glu Asn Leu Asn Leu Phe Asn Ile Thr Tyr Gly LysTyr Asn Leu 20 25 30 Phe Phe Leu Tyr Arg Tyr Xaa 35 230 39 PRT Homosapiens SITE (39) Xaa equals stop translation 230 Met Tyr Ile Phe TyrLeu Tyr Lys Ile Tyr Ile Tyr Thr His Ile Cys 1 5 10 15 Ile Tyr Ile ProLeu Phe Leu Cys Leu Leu Ile Leu Ala Ile Lys Glu 20 25 30 Gly Ala Ala PheAsn Val Xaa 35 231 62 PRT Homo sapiens SITE (62) Xaa equals stoptranslation 231 Met Asn Glu Ser Val Tyr Asp Asp Ser Thr Ser Ser Tyr ThrPro Ser 1 5 10 15 Leu His Ile Leu Gly Cys Leu Leu Leu Leu Phe Leu GlyVal Glu Arg 20 25 30 Ala Leu Glu Pro Phe Ser Gly Leu Cys Ala Ser Leu HisAsp Val Arg 35 40 45 Pro Ile Val Asn Pro Leu Thr Ser Phe Ser Leu Ile TyrXaa 50 55 60 232 198 PRT Homo sapiens SITE (198) Xaa equals stoptranslation 232 Met Cys Thr Gly Lys Cys Ala Arg Cys Val Gly Leu Ser LeuIle Thr 1 5 10 15 Leu Cys Leu Val Cys Ile Val Ala Asn Ala Leu Leu LeuVal Pro Asn 20 25 30 Gly Glu Thr Ser Trp Thr Asn Thr Asn His Leu Ser LeuGln Val Trp 35 40 45 Leu Met Gly Gly Phe Ile Gly Gly Gly Leu Met Val LeuCys Pro Gly 50 55 60 Ile Ala Ala Val Arg Ala Gly Gly Lys Gly Cys Cys GlyAla Gly Cys 65 70 75 80 Cys Gly Asn Arg Cys Arg Met Leu Arg Ser Val PheSer Ser Ala Phe 85 90 95 Gly Val Leu Gly Ala Ile Tyr Cys Leu Ser Val SerGly Ala Gly Leu 100 105 110 Arg Asn Gly Pro Arg Cys Leu Met Asn Gly GluTrp Gly Tyr His Phe 115 120 125 Glu Asp Thr Ala Gly Ala Tyr Leu Leu AsnArg Thr Leu Trp Asp Arg 130 135 140 Cys Glu Ala Pro Pro Arg Val Val ProTrp Asn Val Thr Leu Phe Ser 145 150 155 160 Leu Leu Val Ala Ala Ser CysLeu Glu Ile Val Leu Cys Gly Ile Gln 165 170 175 Leu Val Asn Ala Thr IleGly Val Phe Cys Gly Asp Cys Arg Lys Lys 180 185 190 Gln Asp Thr Pro HisXaa 195 233 62 PRT Homo sapiens SITE (62) Xaa equals stop translation233 Met Ser Gln Leu Phe Leu Ile Met Leu Thr Phe Ile Phe Leu Asn Asn 1 510 15 Met Phe Ile Met His Leu Thr Ser Phe His Gly Lys Arg Val Phe Gly 2025 30 Phe Leu Asn Gln Ser Ser His Met His Ala Phe Pro Leu Pro Arg Trp 3540 45 Thr Thr Ser Ile Phe Ser Val Ser Ile Phe Ile Asn Arg Xaa 50 55 60234 81 PRT Homo sapiens SITE (81) Xaa equals stop translation 234 MetAla Phe Leu Pro Leu Thr Leu Thr Phe Cys Leu Ala Pro Leu Ala 1 5 10 15Pro Leu Leu Pro Ser Ile Trp Gly Pro Thr Pro Ala Ser Cys Val Val 20 25 30Trp Pro Leu Leu Thr Ile Leu Pro Val Pro Ala Gln Ala Ser Pro Ser 35 40 45Thr Asp Thr Ala His Leu Trp Gln Arg Pro Thr Thr Gly Ser Pro Thr 50 55 60Arg Leu Val Arg Pro Leu Pro Arg Pro Gly Leu Pro Pro Met Trp Ala 65 70 7580 Xaa 235 111 PRT Homo sapiens 235 Met Gly Gly Leu Glu Pro Cys Ser ArgLeu Leu Leu Leu Pro Leu Leu 1 5 10 15 Leu Ala Val Gly Leu Arg Pro ValGln Ala Gln Ala Gln Ser Asp Cys 20 25 30 Ser Cys Ser Thr Val Ser Pro GlyVal Leu Ala Gly Ile Val Met Gly 35 40 45 Asp Leu Val Leu Thr Val Leu IleAla Leu Ala Val Tyr Phe Leu Gly 50 55 60 Arg Leu Val Pro Arg Gly Arg GlyAla Ala Glu Ala Thr Arg Lys Gln 65 70 75 80 Arg Ile Thr Glu Thr Glu SerPro Tyr Gln Glu Leu Gln Gly Gln Arg 85 90 95 Ser Asp Val Tyr Ser Asp LeuAsn Thr Gln Arg Pro Tyr Tyr Lys 100 105 110 236 33 PRT Homo sapiens SITE(33) Xaa equals stop translation 236 Met Gln Arg Met Leu Val Leu Leu PhePhe Phe Phe Ser Leu Leu Ala 1 5 10 15 Ile Asn Pro Ala Glu Thr Ile CysGly Tyr Gly Ser Thr Trp Lys Phe 20 25 30 Xaa 237 229 PRT Homo sapiensSITE (134) Xaa equals any of the naturally occurring L-amino acids 237Met Val Leu Gly Leu Phe Val Pro Pro Val Phe Val Val Ser Tyr Ala 1 5 1015 Lys Asp Leu Gly Val Pro Asp Thr Lys Ala Ala Phe Leu Leu Thr Ile 20 2530 Leu Gly Phe Ile Asp Ile Phe Ala Arg Pro Ala Ala Gly Phe Val Ala 35 4045 Gly Leu Gly Lys Val Arg Pro Tyr Ser Val Tyr Leu Phe Ser Phe Ser 50 5560 Met Phe Phe Asn Gly Leu Ala Asp Leu Ala Gly Ser Thr Ala Gly Asp 65 7075 80 Tyr Gly Gly Leu Val Val Phe Cys Ile Phe Phe Gly Ile Ser Tyr Gly 8590 95 Met Val Gly Ala Leu Gln Phe Glu Val Leu Met Ala Ile Val Gly Thr100 105 110 His Lys Phe Ser Ser Ala Ile Gly Leu Val Leu Leu Met Glu AlaVal 115 120 125 Ala Val Leu Val Gly Xaa Pro Ser Gly Gly Lys Leu Leu AspAla Thr 130 135 140 His Val Tyr Met Tyr Val Phe Ile Leu Ala Gly Ala GluVal Leu Thr 145 150 155 160 Ser Ser Leu Ile Leu Leu Leu Gly Asn Phe PheCys Ile Arg Lys Lys 165 170 175 Pro Lys Glu Pro Gln Pro Glu Val Ala AlaAla Glu Glu Glu Lys Leu 180 185 190 His Lys Pro Pro Ala Asp Ser Gly ValAsp Leu Arg Glu Val Glu His 195 200 205 Phe Leu Lys Ala Glu Pro Glu LysAsn Gly Glu Val Val His Thr Pro 210 215 220 Glu Thr Ser Val Xaa 225 238117 PRT Homo sapiens SITE (117) Xaa equals stop translation 238 Met ThrPro Leu Leu Thr Leu Ile Leu Val Val Leu Met Gly Leu Pro 1 5 10 15 LeuAla Gln Ala Leu Asp Cys His Val Cys Ala Tyr Asn Gly Asp Asn 20 25 30 CysPhe Asn Pro Met Arg Cys Pro Ala Met Val Ala Tyr Cys Met Thr 35 40 45 ThrArg Thr Tyr Tyr Thr Pro Thr Arg Met Lys Val Ser Lys Ser Cys 50 55 60 ValPro Arg Cys Phe Glu Thr Val Tyr Asp Gly Tyr Ser Lys His Ala 65 70 75 80Ser Thr Thr Ser Cys Cys Gln Tyr Asp Leu Cys Asn Gly Thr Gly Leu 85 90 95Ala Thr Pro Ala Thr Leu Ala Leu Ala Pro Ile Leu Leu Ala Thr Leu 100 105110 Trp Gly Leu Leu Xaa 115 239 37 PRT Homo sapiens SITE (37) Xaa equalsstop translation 239 Met Leu Thr Trp Leu Asp Leu Asp Leu Leu Phe Cys PheLeu Phe Leu 1 5 10 15 Phe Leu Phe Ile Leu Phe Tyr Phe Leu Gln Leu AsnGlu Phe Trp Gly 20 25 30 Gly Asn Pro Phe Xaa 35 240 58 PRT Homo sapiens240 Met Glu Pro Trp Ser Trp Phe Phe Phe Phe Phe Phe Phe Phe Pro Gln 1 510 15 Arg Thr Cys Gly Cys Ala Leu Cys Val Leu Phe Leu Phe Ser Ile Trp 2025 30 Gly Pro His Gly Lys Glu Leu Leu Asn Ser Phe Leu Tyr Glu Leu Pro 3540 45 Leu Cys Ser Tyr Lys Gly Pro Phe Leu Ser 50 55 241 48 PRT Homosapiens SITE (48) Xaa equals stop translation 241 Met Gln Ser Gly ArgSer Trp Ala Leu Lys Met Val Leu Leu Cys Asn 1 5 10 15 Ser Cys Leu GlyLeu Gly Val Gly Ser Val Gly Pro Ser Met Ser Ser 20 25 30 Leu Phe Gly AlaVal Leu Ser Glu Thr Pro Gly Ser Ser Val Tyr Xaa 35 40 45 242 32 PRT Homosapiens SITE (32) Xaa equals stop translation 242 Met Ile Thr Leu CysIle Phe Leu Leu Phe Lys Val Phe Val Gly Ile 1 5 10 15 Ile Leu His TyrLeu Ile Gly Lys Asn Ile Tyr Val Tyr Ser Val Xaa 20 25 30 243 64 PRT Homosapiens SITE (64) Xaa equals stop translation 243 Met Ala Ser Leu LeuGln Arg Asn Leu Cys Pro Arg Leu Ser Val Cys 1 5 10 15 Leu Val Phe IleGln Val Phe Val Cys Cys Val Glu Gly Gly Gly Arg 20 25 30 Arg Val Lys AlaVal Leu Phe Arg Ala Pro Phe Gly Glu His Ser Arg 35 40 45 Gln Asn Thr LeuVal Ile Pro Ser Gln Thr Gly Leu Gln Ala His Xaa 50 55 60 244 68 PRT Homosapiens SITE (68) Xaa equals stop translation 244 Met Pro Val Tyr AspPhe Asn Trp Trp Tyr Ser Leu Tyr Phe Ile Ile 1 5 10 15 Tyr Ile Ile IleAsn Thr Tyr Ile Phe Lys Ser Val Phe Leu Ala Met 20 25 30 Val Tyr Ser AsnTyr Arg Lys His Phe His Ile Leu Cys Val Cys Val 35 40 45 Cys Val Phe CysSer Asp Glu Gln Asn Leu Leu Phe Thr Gln Phe Tyr 50 55 60 Tyr Leu Ser Xaa65 245 46 PRT Homo sapiens SITE (43) Xaa equals any of the naturallyoccurring L-amino acids 245 Met Ser Asp Lys Leu Ser Pro Ser Thr Val ProLeu Leu Leu Pro Val 1 5 10 15 Leu Phe Lys Val Thr Ile Leu Leu Gln ArgVal Cys Pro Glu Asp Ser 20 25 30 Pro Ser Ser Ser Val Leu Pro Glu Ser ValXaa Arg Glu Xaa 35 40 45 246 43 PRT Homo sapiens SITE (43) Xaa equalsstop translation 246 Met Arg Lys Glu Glu Gly Ile Ala His Leu Ser Ile AlaPhe Phe Val 1 5 10 15 Gln Val Leu Cys Leu Tyr Gln Leu Leu Pro Val IleLeu Pro Gln Phe 20 25 30 Asn Leu Gly Ser Gly Lys Asn Met Asn Arg Xaa 3540 247 32 PRT Homo sapiens SITE (11) Xaa equals any of the naturallyoccurring L-amino acids 247 Met Ile His Val Leu Thr Phe Leu Leu Gln XaaTyr Ile Leu Ile Ser 1 5 10 15 Lys Gly Lys Gly Asp Val Ser Gln Phe ValLys Ser Arg Glu Tyr Xaa 20 25 30 248 24 PRT Homo sapiens SITE (24) Xaaequals stop translation 248 Met Ser Glu Leu Ser Ala Phe Met Phe Ser ThrIle Ile Phe Leu Met 1 5 10 15 Ala Gln Pro Thr Ser Cys Phe Xaa 20 249 80PRT Homo sapiens SITE (36) Xaa equals any of the naturally occurringL-amino acids 249 Met Arg Val Phe Ala Leu Leu Pro Pro Phe His Lys SerThr Val Leu 1 5 10 15 Ser Phe Leu Leu Phe Phe Leu Ser Phe Phe Phe PheArg Gln Gly Leu 20 25 30 Ala Val Ser Xaa Arg Leu Glu Cys Ser Gly Ala IleIle Ala His Cys 35 40 45 Ser Leu Asp Leu Leu Asp Ser Ser Asn Pro Pro AlaLeu Thr Ser Gln 50 55 60 Leu Leu Arg Arg Pro Arg Gln Glu Asp His Leu SerPro Gly Gly Xaa 65 70 75 80 250 16 PRT Homo sapiens SITE (16) Xaa equalsstop translation 250 Met Ser His Cys Ala Trp Leu His Leu Gln Leu Phe LeuSer Leu Xaa 1 5 10 15 251 47 PRT Homo sapiens SITE (47) Xaa equals stoptranslation 251 Met Met Phe Cys Phe Leu Ile Trp Val Val Val Thr Phe ThrTyr Ser 1 5 10 15 Leu Asn Cys Thr Phe Val Leu His Lys Phe Ile Ile PhePro Asn Phe 20 25 30 Lys Lys Val Lys Arg Arg Arg Lys Lys Leu Val Met LysVal Xaa 35 40 45 252 32 PRT Homo sapiens SITE (32) Xaa equals stoptranslation 252 Met Pro Pro Pro Glu Cys Leu Ser Asp Cys Ser Lys Val AlaLeu Val 1 5 10 15 Met Val Leu Phe Leu Phe Leu His Gln Ser Ser Cys TrpAla Ala Xaa 20 25 30 253 36 PRT Homo sapiens SITE (36) Xaa equals stoptranslation 253 Met Ala Ser Ser Val Thr Val Lys Glu Val Cys Val Leu PheAsn Leu 1 5 10 15 Leu Ile Ile Ile Thr Ala Met Val Tyr His Ser Phe ThrLys Tyr Gln 20 25 30 Thr Leu Phe Xaa 35 254 51 PRT Homo sapiens SITE(51) Xaa equals stop translation 254 Met Ile Phe Leu Phe Phe Ile Leu PheGlu Ile Ile Val Thr Leu Trp 1 5 10 15 Leu Thr Pro Thr Tyr Pro Gln AlaPhe Ser Glu Leu Thr Ile Gln Ile 20 25 30 Thr Ala Pro Phe Gly Ser Leu ProGln Gln Leu Tyr Leu His Met Ser 35 40 45 Ile Ile Xaa 50 255 76 PRT Homosapiens 255 Met Phe Phe Leu Leu Ile Leu Cys Trp Leu Leu Cys Leu Ser LeuSer 1 5 10 15 Gly Leu Tyr Pro Arg Leu Leu Asn Pro Gly Gly Trp Leu SerLeu Leu 20 25 30 Ser Phe Gln Met Asp Tyr Gly Trp Ile Leu Pro Trp Gly AlaCys Thr 35 40 45 Val Arg His Gly Lys Pro Gly Met Gly Lys Arg Ser Gly GlySer Leu 50 55 60 Pro His Leu Thr Ala Leu Val Leu Cys Leu Thr Ser 65 7075 256 61 PRT Homo sapiens SITE (61) Xaa equals stop translation 256 MetLeu Leu Ser Asn Leu Ser Leu Ser Leu Gln Pro Leu Leu Phe Leu 1 5 10 15Phe Ser Phe Phe Leu Phe Cys Lys Met Gly Ser Arg Lys Gly Leu Arg 20 25 30His Lys Thr Gln His Phe Ser Ser Met Thr Asp Gln Ile Leu Lys Gly 35 40 45Ser Val Arg Ser Pro Ala Leu Gly Gln Leu His Asp Xaa 50 55 60 257 37 PRTHomo sapiens SITE (37) Xaa equals stop translation 257 Met Tyr Glu ValAsp Lys Lys Ile Tyr Ser Asn Phe Ile Gln Ile Leu 1 5 10 15 Ile Val IleIle Phe Val Leu Tyr Leu Ile Ile Asn Gln Asn Thr Phe 20 25 30 Ala Phe LeuSer Xaa 35 258 43 PRT Homo sapiens SITE (43) Xaa equals stop translation258 Met Cys Ile Leu Pro Leu Met Leu Thr Tyr Pro Ile Leu Pro Lys Val 1 510 15 Val Gly Asn Asn Ile Leu Leu Gly Asp Ser Gly Leu Thr Ser Leu Val 2025 30 Ile Pro Leu Ser Val Val Phe Asn Leu Lys Xaa 35 40 259 39 PRT Homosapiens SITE (39) Xaa equals stop translation 259 Met Ile Leu Val SerLys Leu Phe Phe Gly Phe Ser Leu Met Phe Leu 1 5 10 15 Ile Phe Phe ProLeu Ala Thr Met Thr Val His Val Leu Ile Asn Ile 20 25 30 Gly Arg Ser ArgTyr Lys Xaa 35 260 51 PRT Homo sapiens SITE (51) Xaa equals stoptranslation 260 Met Ser Ile Thr Ser Asn Thr Tyr Phe Phe Leu Leu Gly AlaPhe Lys 1 5 10 15 Ile Leu Ser Ser Ser Tyr Trp Lys Ile His Thr Lys LeuLeu Leu Thr 20 25 30 Ile Val Pro Leu Gln Cys Cys Gly Met Pro Gln Leu IlePro Pro Leu 35 40 45 Gln Leu Xaa 50 261 76 PRT Homo sapiens SITE (76)Xaa equals stop translation 261 Met Phe Thr Thr Arg Phe Pro Lys Leu LeuIle Phe Pro Lys Ile Val 1 5 10 15 Thr Glu Asn Cys Cys Leu Leu Phe CysSer Phe Trp Gly Trp Trp Cys 20 25 30 Trp Leu Gly His Ala Cys Glu Val MetCys Val Ser Asp Leu Thr Asp 35 40 45 Ser Leu Phe Ser Leu Leu Ile Glu ArgAla Leu Phe Thr Leu Phe Ile 50 55 60 Cys Phe Asp Thr Ser Ala Phe Ser ValLeu Ser Xaa 65 70 75 262 45 PRT Homo sapiens SITE (45) Xaa equals stoptranslation 262 Met Thr Ser His Pro Ser Trp Arg Leu Ile Leu Val Thr SerLeu Val 1 5 10 15 Leu Gly Val Glu Pro Glu Glu Ala Pro Gly Glu Ala GlyGlu Gly Ser 20 25 30 Gly Gly Gln Arg Thr Met Asp Pro Glu Gln Lys Trp Xaa35 40 45 263 53 PRT Homo sapiens SITE (53) Xaa equals stop translation263 Met Pro Ser Leu Asn Leu Val Leu Arg Pro Leu Ile Cys Leu Ala Ser 1 510 15 Ile Thr Ser Phe Leu Ile Phe Phe Pro Leu Leu Thr Leu Ile Leu Cys 2025 30 Ser Pro Asn Ser Pro Pro Phe Pro Leu Pro Ala His Pro Glu Arg His 3540 45 Thr His Thr Gln Xaa 50 264 43 PRT Homo sapiens SITE (43) Xaaequals stop translation 264 Met His Ala Leu Ser Tyr Thr His Leu Ser LeuLeu Ser Leu Phe Leu 1 5 10 15 Phe Leu Pro Pro Ser Phe Leu Tyr Tyr AsnLeu Val Ile Leu Phe Phe 20 25 30 Glu Ala Phe Gln Asn Ile Ser His Leu SerXaa 35 40 265 74 PRT Homo sapiens 265 Met Gly His Leu Phe Val Val CysLeu Leu Ser Ser Trp Trp Thr Phe 1 5 10 15 Arg Pro Phe Ala Leu Ala ValThr Val Asn His Val Ala Val Asn Ile 20 25 30 Val Cys Val Ser Ala Trp ThrCys Val Ser Cys Ser Leu Gly Arg Ser 35 40 45 Cys Gly Leu Glu Gly Ser PheLeu Phe Pro Leu Glu Thr Leu Trp Phe 50 55 60 Pro His Met Val Val Leu CysLeu Thr Phe 65 70 266 52 PRT Homo sapiens SITE (52) Xaa equals stoptranslation 266 Met Arg Lys Ser Gly Ala Met Lys Lys Gly Gly Ile Phe SerAla Glu 1 5 10 15 Phe Leu Lys Val Phe Ile Pro Ser Leu Phe Leu Ser HisVal Leu Ala 20 25 30 Leu Gly Leu Gly Ile Tyr Ile Gly Lys Arg Leu Ser ThrPro Ser Ala 35 40 45 Ser Thr Tyr Xaa 50 267 41 PRT Homo sapiens SITE(41) Xaa equals stop translation 267 Met Trp Val Gln Leu Ile Phe Phe PheVal Gln Tyr Gly Asp Ser Leu 1 5 10 15 Thr Ser Ala Phe Phe Pro Phe SerSer Asn Phe Ser Leu Gln Asn Ser 20 25 30 Gly Phe Ser Met His Lys Leu LysXaa 35 40 268 79 PRT Homo sapiens SITE (79) Xaa equals stop translation268 Met Val Cys Phe Gln Ser Asn Lys Pro Ser Thr Ser Thr Trp Arg Gln 1 510 15 Leu Ser Phe Val Phe Val Leu Phe Cys Leu Phe Cys Leu Gly His Ala 2025 30 Phe Leu Ser Leu Pro Phe Tyr Ile Leu Ser Ile Ile Ala Met Cys Leu 3540 45 Glu Gln Trp Ala Phe His Asn Met Asn Ser Leu Tyr His His Glu Trp 5055 60 Glu Val Arg Gly Asn Leu Ile His Val Asp Phe Thr Leu Pro Xaa 65 7075 269 117 PRT Homo sapiens SITE (117) Xaa equals stop translation 269Met Thr His Lys Ser Leu Val Tyr Leu Trp Phe Leu Cys Ser Ser Val 1 5 1015 Ala Leu Ala Leu Gly Ala Leu Thr Val Trp His Ala Val Leu Ile Ser 20 2530 Arg Gly Glu Thr Ser Ile Glu Arg His Ile Asn Lys Lys Glu Arg Arg 35 4045 Arg Leu Gln Ala Lys Gly Arg Val Phe Arg Asn Pro Tyr Asn Tyr Gly 50 5560 Cys Leu Asp Asn Trp Lys Val Phe Leu Gly Val Asp Thr Gly Arg His 65 7075 80 Trp Leu Thr Arg Val Leu Leu Pro Ser Ser His Leu Pro His Gly Asn 8590 95 Gly Met Ser Trp Glu Pro Pro Pro Trp Val Thr Ala His Ser Ala Ser100 105 110 Val Met Ala Val Xaa 115 270 62 PRT Homo sapiens SITE (62)Xaa equals stop translation 270 Met Ser Asn Leu Gln Phe His Leu Leu ProHis Ser Ser Pro Ile Leu 1 5 10 15 Pro Leu Phe Thr Leu Ala Leu Leu LysMet Gln Ile Pro Gly Leu Arg 20 25 30 Leu Ser His Cys Leu Leu Thr Tyr AsnSer Tyr Thr Arg Thr Pro Phe 35 40 45 Leu Leu Pro Ser Ser Glu Ser Tyr LeuVal Phe Glu Ile Xaa 50 55 60 271 98 PRT Homo sapiens SITE (53) Xaaequals any of the naturally occurring L-amino acids 271 Met Leu Pro LeuTyr Phe Leu Gln Pro Tyr Leu Ser Leu Val Ile Phe 1 5 10 15 Ile Met LeuArg Asp Asn Trp His Leu Leu Ala Leu Thr Cys Ser Tyr 20 25 30 Ser Ile IleTrp Arg Leu Ser Pro Asp Thr Asn Pro Ser Pro Ile Ala 35 40 45 Pro Ser ArgHis Xaa Gln Leu Xaa Val Val Ala Ile Ala Pro Leu Glu 50 55 60 Pro Ser ProHis Ser His Met Gln Ser Ile Pro Lys Asn Leu Ala Gln 65 70 75 80 Phe SerSer Ser Gln Met Phe Ser Leu Thr Leu Gln Leu Val Tyr Ile 85 90 95 Ser Ser272 32 PRT Homo sapiens SITE (32) Xaa equals stop translation 272 MetTyr Ile Leu Ser Leu Ser Cys Ser Ile Phe Phe Ser Phe Phe Phe 1 5 10 15Phe Leu Phe Pro Phe Phe Arg Gly Leu Arg Lys Gly Gln Ala Lys Xaa 20 25 30273 15 PRT Homo sapiens Xaa equals stop translation 273 Ala Ser Ser LeuLeu Val Ser Leu Gln Cys Leu Leu Gln Leu Xaa 1 5 10 15 274 37 PRT Homosapiens SITE (37) Xaa equals stop translation 274 Met Cys Phe Ile LeuVal Val Cys Phe Ala Ser Leu Ile Thr Glu Cys 1 5 10 15 Pro Cys His CysLys Cys Cys Arg Asp Val Gly Arg Gly Pro Thr Val 20 25 30 Leu Tyr Glu MetXaa 35 275 57 PRT Homo sapiens SITE (53) Xaa equals any of the naturallyoccurring L-amino acids 275 Met His Arg Leu Trp Ile Gly Pro Ala Phe PheLeu Met Thr Ser Leu 1 5 10 15 Ser Val Ser Gly Ala Val Ile Pro Arg AsnGly Gly Pro Gly Gly Val 20 25 30 Ser Ser Gly Pro Cys Leu Leu Gln Leu LeuCys Gly Gln Ala Gly Ser 35 40 45 Ser Thr Ile Arg Xaa Ile Pro Ser Xaa 5055 276 27 PRT Homo sapiens SITE (27) Xaa equals stop translation 276 MetGlu Ala Val Phe Phe Leu Phe Phe Leu Leu Leu Leu Leu Thr Trp 1 5 10 15Thr Ser Lys Ile Ala Pro Ile Leu Phe Ser Xaa 20 25 277 68 PRT Homosapiens SITE (68) Xaa equals stop translation 277 Asp Trp Gly Phe GlnThr Thr Phe Phe Ser Leu Gly Leu Tyr Leu Phe 1 5 10 15 Thr Ile Trp TrpSer Thr Val Gly Leu Pro Trp Thr Ser Ser Thr Gln 20 25 30 Arg Glu Leu AspMet Lys Leu Glu Ala Ala Ala Leu Glu Gly Lys Phe 35 40 45 Arg Leu Thr TrpThr Ala Gln Ala Met Ala Gly Arg Ile Pro Ser Ser 50 55 60 Trp Gly Pro Xaa65 278 46 PRT Homo sapiens SITE (46) Xaa equals stop translation 278 MetPro Arg Arg Ser Arg Pro Cys Thr Leu Cys Leu Thr Leu Leu Arg 1 5 10 15Arg Ala Leu Ser Ser His Leu Pro Ser Ala Cys Gln Ser Pro Arg Arg 20 25 30Arg Val Gln Gly Gln Val Leu Lys Arg Leu Lys Pro Leu Xaa 35 40 45 279 40PRT Homo sapiens SITE (40) Xaa equals stop translation 279 Met Pro LeuThr Leu Pro Ser Arg Leu Ala Gly Gly Asn Val Phe Leu 1 5 10 15 Ile IlePhe Thr Pro Gly Phe Cys Pro Gly Arg Val Asn Val Glu Ile 20 25 30 Pro GlnArg Met Leu Asp Glu Xaa 35 40 280 11 PRT Homo sapiens SITE (11) Xaaequals stop translation 280 Met Ser Arg Arg Glu Asn Lys Phe Leu Leu Xaa1 5 10 281 11 PRT Homo sapiens SITE (11) Xaa equals stop translation 281Met Ser Arg Arg Glu Asn Lys Phe Leu Leu Xaa 1 5 10 282 47 PRT Homosapiens 282 Met Leu Pro Ile His Leu Gln Trp Ala Cys Ala Phe Arg Ser PheLeu 1 5 10 15 Leu Gly Ile Asp Ser Ser Met Phe Val Leu Phe Gln His ProArg Leu 20 25 30 Lys Asp Thr Lys Ser Ser Arg Val Ile Glu Pro Thr Leu ThrAsn 35 40 45 283 23 PRT Homo sapiens SITE (23) Xaa equals stoptranslation 283 Met Ile Leu Leu Ala Phe Phe Ile Leu Leu Tyr Leu Thr SerPhe Ser 1 5 10 15 Leu Ala Arg Ser Leu Pro Xaa 20 284 21 PRT Homo sapiensSITE (21) Xaa equals stop translation 284 Ser Ser Ser Cys Met Pro ArgLys Leu Asp Trp Phe Ser Lys Lys Val 1 5 10 15 Phe Leu Phe Phe Xaa 20 285122 PRT Homo sapiens 285 Met Gln Ala Leu Pro Pro Gly Phe Lys Gln Phe SerCys Leu Ser Leu 1 5 10 15 Pro Ser Arg Trp Asp Tyr Gly Cys Ala Thr GlnHis Pro Ala Asn Phe 20 25 30 Cys Ile Phe Arg Arg Asp Arg Val Ser His ValGly Gln Ala Gly Leu 35 40 45 Lys Leu Leu Thr Ser Val Asp Pro Pro Ala TrpAla Ser Gln Ser Ala 50 55 60 Gly Ile Thr Gly Lys Ser His Cys Ala Gln LeuHis Cys Cys Cys Phe 65 70 75 80 Leu Leu Leu Val Lys Arg Asp Gln Pro LeuGlu Lys Cys Leu Arg Leu 85 90 95 Phe Lys Gly Arg Ile Leu Cys Arg Gln ProHis Tyr Arg Leu Leu Ser 100 105 110 Asp Glu Cys Pro Gly Leu Leu Gln AsnPro 115 120 286 27 PRT Homo sapiens SITE (27) Xaa equals stoptranslation 286 Met Ile His Leu Ser Arg Phe Tyr Leu Leu Leu Ile Met LeuPro His 1 5 10 15 Val Leu Phe Phe Thr Gly Asp Leu His Ser Xaa 20 25 2878 PRT Homo sapiens SITE (8) Xaa equals stop translation 287 Met Tyr LysCys Trp Tyr Arg Xaa 1 5 288 29 PRT Homo sapiens SITE (2) Xaa equals anyof the naturally occurring L-amino acids 288 Met Xaa Leu Asn Lys Thr LysSer Leu Thr Leu Leu Glu Leu Val Phe 1 5 10 15 Leu Pro Gly Glu Thr ValSer Lys Pro Ser Thr Lys Xaa 20 25 289 65 PRT Homo sapiens 289 Val AspPro Arg Val Arg Arg Phe Trp Glu Asp Pro Glu Tyr Pro Pro 1 5 10 15 ValAla Val Met Ser Arg Leu Met Leu Arg Arg Ile Pro Thr Val Met 20 25 30 SerAsn Thr His Arg Thr Gln Pro Ser Thr Trp Glu Gln Ile Lys Lys 35 40 45 LeuSer Gln Met Val Gly Glu Asn Leu Arg Lys Ala Gly Gln Pro Val 50 55 60 Thr65 290 25 PRT Homo sapiens 290 Val Arg Arg Phe Trp Glu Asp Pro Glu TyrPro Pro Val Ala Val Met 1 5 10 15 Ser Arg Leu Met Leu Arg Arg Ile Pro 2025 291 27 PRT Homo sapiens 291 Ser Asn Thr His Arg Thr Gln Pro Ser ThrTrp Glu Gln Ile Lys Lys 1 5 10 15 Leu Ser Gln Met Val Gly Glu Asn LeuArg Lys 20 25 292 116 PRT Homo sapiens 292 Ser Ala Cys His Ser His ThrVal Phe Asn Trp Ser Glu Gln Asn Gly 1 5 10 15 Gln Met Val Gln Met ValArg Arg Met Ala Arg Val Pro Ile Ile Trp 20 25 30 Asn His Gly Ser Ile GlyAla Pro Gln Pro Gln Met Ile Trp Pro Ile 35 40 45 Val Gly Ala Lys His LysAsp Leu Trp Gln Leu Leu Ile Ala Leu Asn 50 55 60 Lys Ile Lys Ile Trp GluArg Ile Lys Lys His Leu Glu Gly His Ser 65 70 75 80 Ala Asn Leu Ser LeuAsp Ile Ala Lys Tyr Ile Tyr Ile Phe Lys Ala 85 90 95 Ser Gln Ala His LeuThr Leu Met Pro Glu Leu Glu Cys Ser Lys Glu 100 105 110 Leu Gln Thr Asp115 293 25 PRT Homo sapiens 293 Met Ala Arg Val Pro Ile Ile Trp Asn HisGly Ser Ile Gly Ala Pro 1 5 10 15 Gln Pro Gln Met Ile Trp Pro Ile Val 2025 294 32 PRT Homo sapiens 294 Arg Ile Lys Lys His Leu Glu Gly His SerAla Asn Leu Ser Leu Asp 1 5 10 15 Ile Ala Lys Tyr Ile Tyr Ile Phe LysAla Ser Gln Ala His Leu Thr 20 25 30 295 66 PRT Homo sapiens 295 Val PheLeu Gln Gln Gly Leu Thr Gln Arg Ser Val Ile Leu Ile Gly 1 5 10 15 HisIle Cys Gln Phe Trp Leu Ala Ile Met Pro Gly Tyr Asn His Phe 20 25 30 MetThr Gln Leu His Met Leu Ser Gly Leu Asn Ile Tyr His Asn Lys 35 40 45 SerAla Pro Ile Ile Glu Ala Tyr His Pro Gln Lys Ser Ile Cys Lys 50 55 60 GlnAsn 65 296 28 PRT Homo sapiens 296 Ile Gly His Ile Cys Gln Phe Trp LeuAla Ile Met Pro Gly Tyr Asn 1 5 10 15 His Phe Met Thr Gln Leu His MetLeu Ser Gly Leu 20 25 297 58 PRT Homo sapiens 297 Ser Ile Pro Gly ThrPro Asp Leu Asn Ala Arg Thr Gly Val Leu Glu 1 5 10 15 Gly Ala Ala AspArg Leu Ala Ala Ser Asn Pro Leu Lys Trp Ile Lys 20 25 30 Thr Leu Arg SerSer Val Ile Ser Met Met Ile Val Leu Leu Ile Cys 35 40 45 Val Val Cys LeuTyr Ile Val Cys Arg Cys 50 55 298 27 PRT Homo sapiens 298 Val Leu GluGly Ala Ala Asp Arg Leu Ala Ala Ser Asn Pro Leu Lys 1 5 10 15 Trp IleLys Thr Leu Arg Ser Ser Val Ile Ser 20 25 299 75 PRT Homo sapiens 299Leu Thr Val Thr Lys Leu Pro Trp Leu Phe Ile Ala Leu Gln Asn Lys 1 5 1015 Arg Met Gly Thr Ser Trp Glu Gln Ala Pro Lys Ser Gly His Lys Leu 20 2530 Ala Pro Lys Leu Val Ile Asn Lys Ile Ser Ala Ala Leu Ser His Ala 35 4045 Cys Asp Ser Leu Thr Pro Thr Leu Glu Gly Cys Arg Phe Thr Gly Met 50 5560 Arg Ala Arg Asn Asn Trp Pro Thr Gln Gly Gly 65 70 75 300 29 PRT Homosapiens 300 Met Gly Thr Ser Trp Glu Gln Ala Pro Lys Ser Gly His Lys LeuAla 1 5 10 15 Pro Lys Leu Val Ile Asn Lys Ile Ser Ala Ala Leu Ser 20 25301 52 PRT Homo sapiens 301 Ser Thr His Ala Ser Val Gln Lys Lys Asp LeuThr Lys Phe Ser Ala 1 5 10 15 His Ser Trp Leu Lys Lys Lys Lys Thr PheArg Lys Met Ile Met Glu 20 25 30 Glu Ile Phe Leu Asn Leu Ile Lys Asn IleTyr Lys Ser Pro Tyr Ser 35 40 45 Gln Cys Asn Thr 50 302 17 PRT Homosapiens 302 Val Arg Ser Glu Lys Gly Phe Asp Lys Ile Gln Cys Pro Phe MetVal 1 5 10 15 Lys 303 46 PRT Homo sapiens 303 Phe Ser Lys Pro Ser SerTyr Lys Thr Tyr Ile Pro Lys Ile Asn Leu 1 5 10 15 His Phe Tyr Ile LeuLeu Met Asn Ile Trp Glu Thr Ile Lys Ile Val 20 25 30 Pro Leu Asn Asn CysPhe Thr Lys Met Asn Tyr Leu Gly Ile 35 40 45 304 14 PRT Homo sapiens 304Lys Lys Glu Thr Lys Leu Ser Leu Phe Ala Asn Asp Met Ile 1 5 10 305 23PRT Homo sapiens 305 Ser Pro Leu Leu Phe Asn Ile Leu Leu Glu Val Leu SerSer Ala Val 1 5 10 15 Arg Lys Glu Lys Glu Leu Lys 20 306 122 PRT Homosapiens 306 Leu Arg Arg Pro Ser Thr Pro Leu Arg Arg Pro Trp Leu His LeuGln 1 5 10 15 Leu Pro Arg Ile Ser Leu Gly Asp Gln Arg Leu Ala Gln SerAla Glu 20 25 30 Met Tyr His Tyr Gln His Gln Arg Gln Gln Met Leu Ser LeuGlu Arg 35 40 45 His Lys Glu Pro Pro Lys Glu Leu Asp Thr Ala Leu Arg MetArg Arg 50 55 60 Met Arg Thr Glu Thr Ser Arg Cys Thr Ser Ala Arg Ala TrpPro Arg 65 70 75 80 Pro Gly Lys Trp Arg Cys Ala Thr Ile Cys Ser Thr ThrPro His Cys 85 90 95 Pro Arg Pro Cys Arg Pro Pro Ala His Arg Leu His CysHis Asp Leu 100 105 110 Glu Ala Asp Arg Arg Pro Leu Ala Pro Arg 115 120307 60 PRT Homo sapiens 307 Arg Ala Thr Gln Gly Ala Gly His Gly Ser SerAsp Glu Glu Asn Glu 1 5 10 15 Asp Gly Asp Phe Thr Val Tyr Glu Cys ProGly Met Ala Pro Thr Gly 20 25 30 Glu Met Glu Val Arg Asn His Leu Phe AspHis Ala Ala Leu Ser Ala 35 40 45 Pro Leu Pro Ala Pro Ser Ser Pro Leu AlaLeu Pro 50 55 60 308 47 PRT Homo sapiens 308 Lys Ala Glu Tyr Ala Thr AlaLys Ala Leu Ala Thr Pro Ala Ala Thr 1 5 10 15 Pro Asp Leu Ala Trp GlyPro Ala Pro Gly Thr Glu Arg Gly Asp Val 20 25 30 Pro Leu Pro Ala Pro ThrAla Thr Asp Val Val Pro Gly Ala Ala 35 40 45 309 15 PRT Homo sapiens 309Ser Ala Glu Met Tyr His Tyr Gln His Gln Arg Gln Gln Met Leu 1 5 10 15310 11 PRT Homo sapiens 310 Leu Glu Arg His Lys Glu Pro Pro Lys Glu Leu1 5 10 311 12 PRT Homo sapiens 311 Ala Lys Cys Pro Pro Gly Ala His AlaCys Gly Pro 1 5 10 312 9 PRT Homo sapiens 312 Pro Val His Met Ser ProLeu Glu Pro 1 5 313 12 PRT Homo sapiens 313 Trp Cys Arg Leu Gln Arg GluIle Arg Leu Thr Gln 1 5 10 314 18 PRT Homo sapiens 314 Ser Ser Asp GluGlu Asn Glu Asp Gly Asp Phe Thr Val Tyr Glu Cys 1 5 10 15 Pro Gly 315 10PRT Homo sapiens 315 Ala Pro Thr Gly Glu Met Glu Val Arg Asn 1 5 10 31610 PRT Homo sapiens 316 Cys Pro Gly Ser Leu Asp Cys Ala Leu Lys 1 5 10317 60 PRT Homo sapiens 317 Arg Ala Thr Gln Gly Ala Gly His Gly Ser SerAsp Glu Glu Asn Glu 1 5 10 15 Asp Gly Asp Phe Thr Val Tyr Glu Cys ProGly Met Ala Pro Thr Gly 20 25 30 Glu Met Glu Val Arg Asn His Leu Phe AspHis Ala Ala Leu Ser Ala 35 40 45 Pro Leu Pro Ala Pro Ser Ser Pro Leu AlaLeu Pro 50 55 60 318 22 PRT Homo sapiens 318 Asn Glu Asp Gly Asp Phe ThrVal Tyr Glu Cys Pro Gly Met Ala Pro 1 5 10 15 Thr Gly Glu Met Glu Val 20319 159 PRT Homo sapiens SITE (114) Xaa equals any of the naturallyoccurring L-amino acids 319 Arg Pro Thr Arg Pro Ser Ser Ser Cys Val LeuPro Arg Cys Leu Arg 1 5 10 15 Cys Ser Arg Arg Gly Ala Arg Ser Pro ArgArg Ala Pro Gly Leu Ala 20 25 30 Val Pro Cys Cys Pro Gly Gly Gly Ala GluGly Trp Arg Arg Arg Cys 35 40 45 Leu Arg Pro Pro Arg Gly Thr Cys Gly CysCys Gly Cys Cys Ser Pro 50 55 60 Ala Ser Ser Ser Ala Pro Pro Cys Val GluPro Pro Pro Ala Thr Arg 65 70 75 80 Asn Val Ala Ala Cys Pro Gly Ser LeuAsp Cys Ala Leu Lys Lys Arg 85 90 95 Ala Ser Val Leu Leu Val His Met ProVal Gly Leu Pro Ser Ala Leu 100 105 110 Pro Xaa Gly Thr Ala Lys Ala CysPhe Ala Xaa Met Arg Arg Ala Ser 115 120 125 Xaa Gly Gly Arg Ala Gln ProXaa Leu Glu Met Arg Leu Ile Pro Gly 130 135 140 Pro Arg Glu Leu Ala ArgLys Gly Ile Trp Thr Ser Ile Pro Pro 145 150 155 320 25 PRT Homo sapiens320 Arg Cys Leu Arg Cys Ser Arg Arg Gly Ala Arg Ser Pro Arg Arg Ala 1 510 15 Pro Gly Leu Ala Val Pro Cys Cys Pro 20 25 321 34 PRT Homo sapiensSITE (28) Xaa equals any of the naturally occurring L-amino acids 321Gly Ser Leu Asp Cys Ala Leu Lys Lys Arg Ala Ser Val Leu Leu Val 1 5 1015 His Met Pro Val Gly Leu Pro Ser Ala Leu Pro Xaa Gly Thr Ala Lys 20 2530 Ala Cys 322 25 PRT Homo sapiens 322 Asp Ser His Gln Ala Arg Ser ArgArg Leu Glu Ala Leu Trp Ser Pro 1 5 10 15 Ser Leu Gly Glu Val Ser SerSer Thr 20 25 323 8 PRT Homo sapiens 323 Arg Ser Cys Lys Glu Ile Lys Asp1 5 324 13 PRT Homo sapiens 324 Gly Gly Gly Trp Thr Leu Val Ala Ser ValHis Glu Asn 1 5 10 325 19 PRT Homo sapiens 325 Ala Asp Tyr Pro Glu GlyAsp Gly Asn Trp Ala Asn Tyr Asn Thr Phe 1 5 10 15 Gly Ser Ala 326 14 PRTHomo sapiens 326 Ala Thr Ser Asp Asp Tyr Lys Asn Pro Gly Tyr Tyr Asp Ile1 5 10 327 11 PRT Homo sapiens 327 Cys Ile Gly Gly Gly Gly Tyr Phe ProGlu Ala 1 5 10 328 11 PRT Homo sapiens 328 Glu Ile Thr Glu Ala Ala ValLeu Leu Phe Tyr 1 5 10 329 6 PRT Homo sapiens 329 Asp Ser Asp Lys IleThr 1 5 330 8 PRT Homo sapiens 330 Tyr Gln Thr Phe Cys Asp Met Thr 1 5331 154 PRT Homo sapiens 331 Met Gly Lys Arg Ala His Glu Val Arg Arg ProPro His Ser Arg Pro 1 5 10 15 Leu His Gly Thr Pro Ala Gly Trp Val LeuAsp Pro Ser Gly Tyr Lys 20 25 30 Asp Val Thr Gln Asp Ala Glu Val Met GluVal Leu Gln Asn Leu Tyr 35 40 45 Arg Thr Lys Ser Phe Leu Phe Val Gly CysGly Glu Thr Leu Arg Asp 50 55 60 Gln Ile Phe Gln Ala Leu Phe Leu Tyr SerVal Pro Asn Lys Val Asp 65 70 75 80 Leu Glu His Tyr Met Leu Val Leu LysGlu Asn Glu Asp His Phe Phe 85 90 95 Lys His Gln Ala Asp Met Leu Leu HisGly Ile Lys Val Val Ser Tyr 100 105 110 Gly Asp Cys Phe Asp His Phe ProGly Tyr Val Gln Asp Leu Ala Thr 115 120 125 Gln Ile Cys Lys Gln Gln SerPro Gly His Leu Tyr Ser Asn Ser Trp 130 135 140 Ser Ala Thr Pro Asp GlyArg Gly Gly Pro 145 150 332 26 PRT Homo sapiens 332 Val Leu Asp Pro SerGly Tyr Lys Asp Val Thr Gln Asp Ala Glu Val 1 5 10 15 Met Glu Val LeuGln Asn Leu Tyr Arg Thr 20 25 333 26 PRT Homo sapiens 333 Tyr Ser ValPro Asn Lys Val Asp Leu Glu His Tyr Met Leu Val Leu 1 5 10 15 Lys GluAsn Glu Asp His Phe Phe Lys His 20 25 334 25 PRT Homo sapiens 334 AspLeu Ala Thr Gln Ile Cys Lys Gln Gln Ser Pro Gly His Leu Tyr 1 5 10 15Ser Asn Ser Trp Ser Ala Thr Pro Asp 20 25 335 121 PRT Homo sapiens 335Arg Arg Met Lys Thr Ile Ser Leu Ser Ile Arg Gln Ile Cys Phe Cys 1 5 1015 Thr Glu Ser Lys Leu Tyr Pro Thr Gly Thr Val Leu Thr Thr Phe Gln 20 2530 Asp Met Cys Lys Thr Leu Pro Leu Arg Ser Ala Asn Ser Lys Ala Gln 35 4045 Asp Ile Cys Thr Arg Ile His Gly Val Pro Leu Leu Met Gly Glu Glu 50 5560 Ala His Asp Ser Asp Ser His Ala Ser Asp Arg Gly His His Thr Met 65 7075 80 Leu Pro Leu Pro Ala Gly Ser Phe Ser Glu Ser Ser His Gln Ala Trp 8590 95 Glu Val Glu Met Leu Ile Ala Trp Thr Ala Pro His Tyr Trp Val Met100 105 110 His Ala Arg Thr Val Gln Arg Gly Ser 115 120 336 27 PRT Homosapiens 336 Thr Glu Ser Lys Leu Tyr Pro Thr Gly Thr Val Leu Thr Thr PheGln 1 5 10 15 Asp Met Cys Lys Thr Leu Pro Leu Arg Ser Ala 20 25 337 27PRT Homo sapiens 337 Leu Met Gly Glu Glu Ala His Asp Ser Asp Ser His AlaSer Asp Arg 1 5 10 15 Gly His His Thr Met Leu Pro Leu Pro Ala Gly 20 25338 86 PRT Homo sapiens 338 Leu Cys Ala Val Glu Lys Thr Arg Thr Phe ThrArg Gly Asp Cys Gly 1 5 10 15 Pro Asn Arg His His Lys His Val Leu LysAla Lys Asp Asn Asn His 20 25 30 Ile Gln Arg His Gln Phe Ser Ser Thr LeuGlu Phe Ser Ser Asn Ser 35 40 45 Thr Asp Gly Leu Lys Tyr Ile Cys Val TyrLeu Tyr Val Cys Thr His 50 55 60 Pro Cys Ile Tyr Ile Tyr Leu Ser Ala HisThr Leu His Met Tyr Thr 65 70 75 80 His Tyr Leu Cys Lys Ile 85 339 30PRT Homo sapiens 339 Ser Ser Thr Leu Glu Phe Ser Ser Asn Ser Thr Asp GlyLeu Lys Tyr 1 5 10 15 Ile Cys Val Tyr Leu Tyr Val Cys Thr His Pro CysIle Tyr 20 25 30 340 69 PRT Homo sapiens 340 Ser Thr Ser Val Cys Ile CysThr Cys Ala His Thr His Val Tyr Ile 1 5 10 15 Phe Ile Tyr Leu His ThrHis Tyr Ile Cys Ile His Thr Ile Tyr Val 20 25 30 Lys Tyr Asn Ile Cys IleMet His Ile Asn Ser Asn Lys Cys Ile Cys 35 40 45 Val Ile Phe Lys Ile GluGln Leu Tyr Leu Glu Val Val Asn Ala Glu 50 55 60 Asn Trp Phe Tyr Cys 65341 31 PRT Homo sapiens 341 Ile His Thr Ile Tyr Val Lys Tyr Asn Ile CysIle Met His Ile Asn 1 5 10 15 Ser Asn Lys Cys Ile Cys Val Ile Phe LysIle Glu Gln Leu Tyr 20 25 30 342 9 PRT Homo sapiens 342 Asn Ser Ala ValThr Val Gln Met Ala 1 5 343 8 PRT Homo sapiens 343 Thr Lys Thr Ser ThrPro Leu Arg 1 5 344 14 PRT Homo sapiens 344 Val Cys Ile Pro Gly Ala AlaGly Leu Ser Val Leu Leu Gly 1 5 10 345 45 PRT Homo sapiens 345 Ser IleLeu Pro Val Glu Met Ala Ala Ala Val Ala Gly Met Leu Arg 1 5 10 15 GlyGly Leu Leu Pro Gln Ala Gly Arg Leu Pro Thr Leu Gln Thr Val 20 25 30 ArgTyr Gly Ser Lys Ala Val Thr Arg His Arg Arg Val 35 40 45 346 26 PRT Homosapiens 346 Ala Gly Met Leu Arg Gly Gly Leu Leu Pro Gln Ala Gly Arg LeuPro 1 5 10 15 Thr Leu Gln Thr Val Arg Tyr Gly Ser Lys 20 25 347 24 PRTHomo sapiens 347 Ala Arg Ala Gly Gln Met Gln Asn Leu Glu Ser Ala Arg AlaGly Arg 1 5 10 15 Ser Val Ser Thr Gln Thr Gly Ser 20 348 300 PRT Homosapiens SITE (4) Xaa equals any of the naturally occurring L-amino acids348 Lys His Glu Xaa His Gln Val Ser Asp Gly Ala Leu Arg Cys Phe Ala 1 510 15 Ser Leu Ala Asp Arg Phe Thr Arg Arg Gly Val Asp Pro Ala Pro Leu 2025 30 Ala Lys His Gly Leu Thr Glu Glu Leu Leu Ser Arg Met Ala Ala Ala 3540 45 Gly Gly Thr Val Ser Gly Pro Ser Ser Ala Cys Lys Pro Xaa Arg Ser 5055 60 Thr Thr Gly Ala Pro Ser Thr Thr Ala Asp Ser Lys Leu Ser Asn Gln 6570 75 80 Val Ser Thr Ile Val Ser Leu Leu Ser Thr Leu Cys Arg Gly Ser Pro85 90 95 Val Val Thr His Asp Leu Leu Arg Ser Glu Leu Pro Asp Ser Ile Glu100 105 110 Ser Ala Leu Gln Gly Asp Glu Arg Cys Val Leu Asp Thr Met ArgLeu 115 120 125 Val Asp Phe Leu Leu Val Leu Leu Phe Glu Gly Arg Lys AlaLeu Pro 130 135 140 Lys Ser Ser Ala Gly Ser Thr Gly Arg Ile Pro Gly LeuArg Arg Leu 145 150 155 160 Asp Ser Ser Gly Glu Arg Ser His Arg Gln LeuIle Asp Cys Ile Arg 165 170 175 Ser Lys Asp Thr Asp Ala Leu Ile Asp AlaIle Asp Thr Gly Ala Phe 180 185 190 Glu Val Asn Phe Met Asp Asp Val GlyGln Thr Leu Leu Asn Trp Ala 195 200 205 Ser Ala Phe Gly Thr Gln Glu MetVal Glu Phe Leu Cys Glu Arg Gly 210 215 220 Ala Asp Val Asn Arg Gly GlnArg Ser Ser Ser Leu His Tyr Ala Ala 225 230 235 240 Cys Phe Gly Arg ProGln Val Ala Lys Thr Leu Leu Arg His Gly Ala 245 250 255 Asn Pro Asp LeuArg Asp Glu Asp Gly Lys Thr Pro Leu Asp Lys Ala 260 265 270 Arg Glu ArgGly His Ser Glu Val Val Ala Ile Leu Gln Ser Pro Gly 275 280 285 Asp TrpMet Cys Pro Val Asn Lys Gly Asp Asp Lys 290 295 300 349 17 PRT Homosapiens 349 Pro Leu Asp Lys Ala Arg Glu Arg Gly His Ser Glu Val Val AlaIle 1 5 10 15 Leu 350 15 PRT Homo sapiens 350 Ala Lys Thr Leu Leu ArgHis Gly Ala Asn Pro Asp Leu Arg Asp 1 5 10 15 351 54 PRT Homo sapiensSITE (49) Xaa equals any of the naturally occurring L-amino acids 351Gly Arg Gly Arg Ala Trp Leu Cys Arg Arg Pro Val Gly Ser Trp Ile 1 5 1015 Gly Ala Val Trp Asn Asp Lys Pro Asp Lys Glu Thr Phe Lys Lys Pro 20 2530 Trp Gln Met Trp Thr Gln Ile His Cys Trp Asn Gly Tyr Arg Trp Asp 35 4045 Xaa Xaa Asp Xaa Lys Asp 50 352 23 PRT Homo sapiens 352 Ser Trp IleGly Ala Val Trp Asn Asp Lys Pro Asp Lys Glu Thr Phe 1 5 10 15 Lys LysPro Trp Gln Met Trp 20 353 30 PRT Homo sapiens SITE (19) Xaa equals anyof the naturally occurring L-amino acids 353 Lys Thr Met Ala Asp Val AspPro Asp Thr Leu Leu Glu Trp Leu Gln 1 5 10 15 Met Gly Xaa Gly Arg XaaLys Gly His Ala Thr Asn Thr Pro 20 25 30 354 34 PRT Homo sapiens 354 ArgGly Val Asp Pro Ala Pro Leu Ala Lys His Gly Leu Thr Glu Glu 1 5 10 15Leu Leu Ser Arg Met Ala Ala Ala Gly Gly Thr Val Ser Gly Pro Ser 20 25 30Ser Ala 355 31 PRT Homo sapiens 355 Arg Ser Thr Thr Gly Ala Pro Ser ThrThr Ala Asp Ser Lys Leu Ser 1 5 10 15 Asn Gln Val Ser Thr Ile Val SerLeu Leu Ser Thr Leu Cys Arg 20 25 30 356 34 PRT Homo sapiens 356 Phe GluVal Asn Phe Met Asp Asp Val Gly Gln Thr Leu Leu Asn Trp 1 5 10 15 AlaSer Ala Phe Gly Thr Gln Glu Met Val Glu Phe Leu Cys Glu Arg 20 25 30 GlyAla 357 28 PRT Homo sapiens 357 Glu Asp Gly Lys Thr Pro Leu Asp Lys AlaArg Glu Arg Gly His Ser 1 5 10 15 Glu Val Val Ala Ile Leu Gln Ser ProGly Asp Trp 20 25 358 15 PRT Homo sapiens 358 Thr Arg Pro Thr Met ProAsn Phe Leu Trp Phe Pro Lys Cys Ala 1 5 10 15 359 44 PRT Homo sapiens359 Leu Pro Pro Cys Leu Ala Gln Ile Phe Pro Phe Phe Ser Ser Gly Thr 1 510 15 Asn Leu Thr Phe Cys Phe Phe Val Phe Val Phe Val Phe Val Phe Ala 2025 30 Glu Leu Asp Tyr Arg Asn Ser Tyr Glu Ile Glu Tyr 35 40 360 9 PRTHomo sapiens 360 Leu Lys Cys Thr Ile Tyr Gly Gly Ala 1 5 361 56 PRT Homosapiens 361 His Val Leu Trp Ser Leu Leu Ser Ala Cys Trp Thr Gln Phe LeuVal 1 5 10 15 Tyr Phe Cys Cys Leu Met Ile Leu Gln Arg Thr Phe Pro ProArg Ala 20 25 30 Leu Arg Thr Ser Pro Trp Leu Ser Asn Pro Met Gly Val LysGly Lys 35 40 45 Lys Lys Lys Gly Thr Phe Met Glu 50 55 362 30 PRT Homosapiens 362 Phe Leu Val Tyr Phe Cys Cys Leu Met Ile Leu Gln Arg Thr PhePro 1 5 10 15 Pro Arg Ala Leu Arg Thr Ser Pro Trp Leu Ser Asn Pro Met 2025 30 363 52 PRT Homo sapiens SITE (26) Xaa equals any of the naturallyoccurring L-amino acids 363 Asp Cys Asn Arg Asp Tyr His Lys Ala Phe GlyAsn Leu Arg Ser Pro 1 5 10 15 Gly Trp Pro Asp Asn Tyr Asp Asn Asp XaaAsp Cys Xaa Val Thr Leu 20 25 30 Thr Ala Pro Gln Asn His His Ser Gly IleVal Glu Asn Ala Glu Thr 35 40 45 Ile Ser Trp Arg 50 364 15 PRT Homosapiens 364 Phe Gly Asn Leu Arg Ser Pro Gly Trp Pro Asp Asn Tyr Asp Asn1 5 10 15 365 16 PRT Homo sapiens SITE (6) Xaa equals any of thenaturally occurring L-amino acids 365 Ala Pro Gln Asn His Xaa Leu LysCys Arg Asn Asp Phe Leu Glu Val 1 5 10 15 366 7 PRT Homo sapiens 366 AlaSer Phe Tyr Arg Thr Ser 1 5 367 26 PRT Homo sapiens 367 Lys Ala Asp ValLys Trp His Met Cys Leu Gln Ser Pro Leu Cys Gly 1 5 10 15 Leu Phe CysSer Ile Glu Gly Val Leu Lys 20 25 368 218 PRT Homo sapiens SITE (59) Xaaequals any of the naturally occurring L-amino acids 368 Ala Cys Met AsnPro Ala Met Cys Phe Val Cys Ala Cys Pro His Thr 1 5 10 15 Gly Ser ThrPro Glu Lys Ala Ile Leu Gln Gly Arg Leu Ile Ser Leu 20 25 30 Gly Thr SerLeu Ser Pro Ala Ser Asn Gly Ser Gly Gln Gln Ser Phe 35 40 45 Ser Ile CysMet Ile Asn Pro Ser Leu Pro Xaa Ser Thr Ser Ser His 50 55 60 His Leu PheSer Val Leu Thr Gly Asp Leu Asp Ser Tyr Ser Gln Arg 65 70 75 80 Lys LeuLys Pro Thr Ser Arg Lys Ser Phe Leu Leu Pro Lys Thr Gln 85 90 95 Thr TyrXaa Val Xaa His Pro Ser Ser Pro Pro Leu Val Leu Val Gln 100 105 110 HisArg Ser Pro Leu Ser Thr Tyr Pro Lys Pro Val Pro Ser Cys Cys 115 120 125Ala Leu Asp Leu Ile Ser Val Ile Ala Leu Glu Thr Phe Leu Val Tyr 130 135140 Ile His Leu Phe Pro Ser Ile Asp Leu Ser Tyr Trp Ile Leu Ser Met 145150 155 160 Leu Gln Pro Leu Leu Leu Ile Lys Gln Gln Ser Thr Lys Thr LeuSer 165 170 175 Leu Asn Cys Met Leu Tyr Ser Ser Tyr Tyr Leu Ile Ser PheLeu Ser 180 185 190 Phe Lys Ala Lys Val Leu Arg Arg Gly Gly Asn Ile LeuHis His Phe 195 200 205 Phe Thr Ser Tyr Ser Phe Phe Asn Thr Tyr 210 215369 28 PRT Homo sapiens 369 Cys Pro His Thr Gly Ser Thr Pro Glu Lys AlaIle Leu Gln Gly Arg 1 5 10 15 Leu Ile Ser Leu Gly Thr Ser Leu Ser ProAla Ser 20 25 370 24 PRT Homo sapiens 370 Gln His Arg Ser Pro Leu SerThr Tyr Pro Lys Pro Val Pro Ser Cys 1 5 10 15 Cys Ala Leu Asp Leu IleSer Val 20 371 29 PRT Homo sapiens 371 Ile Lys Gln Gln Ser Thr Lys ThrLeu Ser Leu Asn Cys Met Leu Tyr 1 5 10 15 Ser Ser Tyr Tyr Leu Ile SerPhe Leu Ser Phe Lys Ala 20 25 372 24 PRT Homo sapiens 372 Lys Tyr LeuVal Ser Ser Val Leu Pro Thr Ile Ser Met Ala Arg Ser 1 5 10 15 Leu IleSer Ala Leu Arg Ser Gly 20 373 27 PRT Homo sapiens 373 Met Arg Thr LeuPhe Gly Ala Val Arg Ala Pro Phe Ser Ser Leu Thr 1 5 10 15 Leu Leu LeuIle Thr Pro Ser Pro Ser Pro Leu 20 25 374 10 PRT Homo sapiens 374 MetAla Tyr Ala Phe His Arg Thr Ser Thr 1 5 10 375 22 PRT Homo sapiens 375Leu Lys Ser Thr Tyr Thr Leu Leu Ser Ile Leu Trp Phe Leu Val Leu 1 5 1015 Ile Pro Val Glu Gly Asn 20 376 18 PRT Homo sapiens 376 Gly Pro LeuLeu Ala Ser His Ala Thr Leu Cys Phe Ser Leu Gly Ser 1 5 10 15 Lys Phe377 10 PRT Homo sapiens 377 Thr Val Trp Gly Ile Leu Pro Arg Lys Arg 1 510 378 20 PRT Homo sapiens 378 Ala Ser Ile Asp Thr Trp Pro Gly Arg ArgSer Gly Gly Met Ile Val 1 5 10 15 Ile Thr Ser Ile 20 379 41 PRT Homosapiens 379 Gly Ser Pro Gln Ala Glu Thr Arg Trp Ser Asp Pro Ile Ala LeuHis 1 5 10 15 Gln Gly Lys Ser Pro Ala Ser Ile Asp Thr Trp Pro Gly ArgArg Ser 20 25 30 Gly Gly Met Ile Val Ile Thr Ser Ile 35 40 380 43 PRTHomo sapiens SITE (2) Xaa equals any of the naturally occurring L-aminoacids 380 Val Xaa Asp Ile Thr Phe Asp Pro Asp Thr Ala His Lys Tyr LeuArg 1 5 10 15 Leu Gln Glu Glu Asn Arg Lys Val Thr Asn Thr Thr Pro TrpGlu His 20 25 30 Pro Tyr Pro Asp Leu Pro Ser Arg Phe Leu His 35 40 38119 PRT Homo sapiens 381 Leu Tyr Leu His Arg Tyr Tyr Phe Glu Val Glu IlePhe Gly Ala Gly 1 5 10 15 Thr Tyr Val 382 22 PRT Homo sapiens 382 SerCys Ile Ser Gly Asn Asn Phe Ser Trp Ser Leu Gln Trp Asn Gly 1 5 10 15Lys Glu Phe Thr Ala Trp 20 383 17 PRT Homo sapiens 383 Thr Pro Leu LysAla Gly Pro Phe Trp Ser Ser Gly Ser Ile Leu Thr 1 5 10 15 Ser 384 39 PRTHomo sapiens SITE (32) Xaa equals any of the naturally occurring L-aminoacids 384 Ser Val Ser Glu Val Lys Ala Val Ala Glu Met Gln Phe Gly GluLeu 1 5 10 15 Leu Ala Ala Val Arg Lys Ala Gln Ala Asn Val Met Leu PheLeu Xaa 20 25 30 Glu Lys Glu Gln Ala Ala Leu 35 385 43 PRT Homo sapiens385 Glu Lys Ser Lys Gln Glu Leu Glu Thr Met Ala Ala Ile Ser Asn Thr 1 510 15 Val Gln Phe Leu Glu Glu Tyr Cys Lys Phe Lys Asn Thr Glu Asp Ile 2025 30 Thr Phe Pro Ser Val Tyr Ile Gly Leu Lys Asp 35 40 386 29 PRT Homosapiens SITE (26) Xaa equals any of the naturally occurring L-aminoacids 386 Leu Glu Asn Tyr Lys Lys Lys Leu Gln Glu Phe Ser Lys Glu GluGlu 1 5 10 15 Tyr Asp Ile Arg Thr Gln Val Ser Ala Xaa Val Gln Arg 20 25387 38 PRT Homo sapiens 387 Gly Val Tyr Ile Asp Phe Pro Gly Gly Ile LeuSer Phe Tyr Gly Val 1 5 10 15 Glu Tyr Asp Ser Met Thr Leu Val His LysPhe Ala Cys Lys Phe Ser 20 25 30 Glu Pro Val Tyr Ala Ala 35 388 10 PRTHomo sapiens 388 Gly Thr Val Ser Arg Glu Arg Arg Ala Gly 1 5 10 389 82PRT Homo sapiens 389 His Gly Asp Pro Thr Gln Ser Trp Pro Phe Leu Glu LeuGly Val Tyr 1 5 10 15 Ile Asp Phe Pro Gly Gly Ile Leu Ser Phe Tyr GlyVal Glu Tyr Asp 20 25 30 Ser Met Thr Leu Val His Lys Phe Ala Cys Lys PheSer Glu Pro Val 35 40 45 Tyr Ala Ala Phe Trp Leu Ser Lys Lys Glu Asn AlaIle Arg Ile Val 50 55 60 Asp Leu Gly Glu Glu Pro Glu Lys Pro Ala Pro SerLeu Val Gly Thr 65 70 75 80 Ala Pro 390 30 PRT Homo sapiens 390 Ser PheTyr Gly Val Glu Tyr Asp Ser Met Thr Leu Val His Lys Phe 1 5 10 15 AlaCys Lys Phe Ser Glu Pro Val Tyr Ala Ala Phe Trp Leu 20 25 30 391 337 PRTHomo sapiens SITE (65) Xaa equals any of the naturally occurring L-aminoacids 391 Ala Glu Leu Gln Cys Thr Gln Leu Asp Leu Glu Arg Lys Leu LysLeu 1 5 10 15 Asn Glu Asn Ala Ile Ser Arg Leu Gln Ala Asn Gln Lys SerVal Leu 20 25 30 Val Ser Val Ser Glu Val Lys Ala Val Ala Glu Met Gln PheGly Glu 35 40 45 Leu Leu Ala Ala Val Arg Lys Ala Gln Ala Asn Val Met LeuPhe Leu 50 55 60 Xaa Glu Lys Glu Gln Ala Ala Leu Ser Gln Ala Asn Gly IleLys Ala 65 70 75 80 His Leu Glu Tyr Lys Ser Ala Glu Met Glu Lys Ser LysGln Glu Leu 85 90 95 Glu Thr Met Ala Ala Ile Ser Asn Thr Val Gln Phe LeuGlu Glu Tyr 100 105 110 Cys Lys Phe Lys Asn Thr Glu Asp Ile Thr Phe ProSer Val Tyr Ile 115 120 125 Gly Leu Lys Asp Lys Leu Ser Gly Ile Arg LysVal Ile Thr Glu Ser 130 135 140 Thr Val His Leu Ile Xaa Xaa Leu Glu AsnTyr Lys Lys Lys Leu Gln 145 150 155 160 Glu Phe Ser Lys Glu Glu Glu TyrAsp Ile Arg Thr Gln Val Ser Ala 165 170 175 Xaa Val Gln Arg Lys Tyr TrpThr Ser Lys Pro Glu Pro Ser Thr Arg 180 185 190 Glu Gln Phe Leu Gln TyrVal Xaa Asp Ile Thr Phe Asp Pro Asp Thr 195 200 205 Ala His Lys Tyr LeuArg Leu Gln Glu Glu Asn Arg Lys Val Thr Asn 210 215 220 Thr Thr Pro TrpGlu His Pro Tyr Pro Asp Leu Pro Ser Arg Phe Leu 225 230 235 240 His TrpArg Gln Val Leu Ser Gln Gln Ser Leu Tyr Leu His Arg Tyr 245 250 255 TyrPhe Glu Val Glu Ile Phe Gly Ala Gly Thr Tyr Val Gly Leu Thr 260 265 270Cys Lys Gly Ile Asp Xaa Lys Gly Glu Glu Arg Xaa Ser Cys Ile Ser 275 280285 Gly Asn Asn Phe Ser Trp Ser Leu Gln Trp Asn Gly Lys Glu Phe Thr 290295 300 Ala Trp Tyr Ser Asp Met Glu Thr Pro Leu Lys Ala Gly Pro Phe Trp305 310 315 320 Ser Ser Gly Ser Ile Leu Thr Ser Gln Glu Gly Ser Phe ProSer Met 325 330 335 Ala 392 301 PRT Homo sapiens SITE (166) Xaa equalsany of the naturally occurring L-amino acids 392 Arg Thr Ala Pro Tyr GlyAla Lys Glu Ser Ser Trp Arg Met Phe Ser 1 5 10 15 Phe Arg Asp Pro IleGly Phe Gln Lys Pro Ala Thr Ile Ser Ser Tyr 20 25 30 Phe Cys Pro Gln IleThr Leu Lys Cys Lys Ser His His Cys Ser Trp 35 40 45 Gln Arg Ser Gly IleTrp Leu Leu Glu Ser Arg Glu Gln Ser Pro Pro 50 55 60 Arg Thr Val Leu AlaSer Arg Val Pro Leu Pro Asp Leu Gln Ser Gly 65 70 75 80 Trp Arg Phe ProSer Trp Lys Ala Arg Arg Gln His Arg Leu Val Leu 85 90 95 Lys Thr Cys ArgGln Thr Cys Glu Pro Glu Ser Trp Asn His Thr Leu 100 105 110 Arg His ArgArg Lys Gly Ser Leu Leu Gly Ser Gln Tyr Arg Pro Arg 115 120 125 Ala ProGlu Arg Ala Ser Phe Glu Trp Gly Leu His Val Thr Val Pro 130 135 140 GlyArg Glu Leu Leu Pro Val Pro Leu Glu Ala Pro Gly Glu Val Val 145 150 155160 Ser Gly Asn Ala Thr Xaa Ala Leu Leu Pro Phe Xaa Val Asp Ala Phe 165170 175 Ala Gly Gln Ala Asn Ile Gly Ala Cys Pro Glu Asp Leu His Leu Lys180 185 190 Ile Val Pro Val Gln Val Gln Thr Leu Leu Gly Gln His Leu ProPro 195 200 205 Val Gln Glu Pro Ala Gly Glu Val Arg Val Gly Met Leu ProGly Arg 210 215 220 Gly Val Gly Asp Leu Ala Val Leu Leu Leu Gln Pro GluIle Leu Val 225 230 235 240 Cys Cys Val Arg Val Glu Arg Asp Val Xaa HisIle Leu Glu Glu Leu 245 250 255 Phe Pro Gly Ala Gly Leu Arg Phe Gly SerPro Ile Phe Ala Leu Asn 260 265 270 Asn Gly Arg His Leu Ser Ser Asp ValIle Leu Leu Phe Leu Gly Lys 275 280 285 Leu Leu Glu Leu Phe Leu Ile ValLeu Gln Xaa Xaa Asp 290 295 300 393 196 PRT Homo sapiens 393 Ser Lys IleLys Tyr Asp Trp Tyr Gln Thr Glu Ser Gln Val Val Ile 1 5 10 15 Thr LeuMet Ile Lys Asn Val Gln Lys Asn Asp Val Asn Val Glu Phe 20 25 30 Ser GluLys Glu Leu Ser Ala Leu Val Lys Leu Pro Ser Gly Glu Asp 35 40 45 Tyr AsnLeu Lys Leu Glu Leu Leu His Pro Ile Ile Pro Glu Gln Ser 50 55 60 Thr PheLys Val Leu Ser Thr Lys Ile Glu Ile Lys Leu Lys Lys Pro 65 70 75 80 GluAla Val Arg Trp Glu Lys Leu Glu Gly Gln Gly Asp Val Pro Thr 85 90 95 ProLys Gln Phe Val Ala Asp Val Lys Asn Leu Tyr Pro Ser Ser Ser 100 105 110Pro Tyr Thr Arg Asn Trp Asp Lys Leu Val Gly Glu Ile Lys Glu Glu 115 120125 Glu Lys Asn Glu Lys Leu Glu Gly Asp Ala Ala Leu Asn Arg Leu Phe 130135 140 Gln Gln Ile Tyr Ser Asp Gly Ser Asp Glu Val Lys Arg Ala Met Asn145 150 155 160 Lys Ser Phe Met Glu Ser Gly Gly Thr Val Leu Ser Thr AsnTrp Ser 165 170 175 Asp Val Gly Lys Arg Lys Val Glu Ile Asn Pro Pro AspAsp Met Glu 180 185 190 Trp Lys Lys Tyr 195 394 39 PRT Homo sapiens 394Gly Asp Ala Ala Leu Asn Arg Leu Phe Gln Gln Ile Tyr Ser Asp Gly 1 5 1015 Ser Asp Glu Val Lys Arg Ala Met Asn Lys Ser Phe Met Glu Ser Gly 20 2530 Gly Thr Val Leu Ser Thr Asn 35 395 23 PRT Homo sapiens 395 Asp TrpTyr Gln Thr Glu Ser Gln Val Val Ile Thr Leu Met Ile Lys 1 5 10 15 AsnVal Gln Lys Asn Asp Val 20 396 146 PRT Homo sapiens SITE (9) Xaa equalsany of the naturally occurring L-amino acids 396 Met Ala Ala Ala Ala AlaGly Thr Xaa Xaa Ser Gln Arg Phe Phe Gln 1 5 10 15 Ser Phe Ser Asp AlaLeu Ile Asp Glu Asp Pro Gln Ala Ala Leu Glu 20 25 30 Glu Leu Thr Lys AlaLeu Glu Gln Lys Pro Asp Asp Ala Gln Tyr Tyr 35 40 45 Cys Gln Arg Ala TyrCys His Ile Leu Leu Gly Asn Tyr Cys Val Ala 50 55 60 Val Ala Asp Ala LysLys Ser Leu Glu Leu Asn Pro Asn Asn Ser Thr 65 70 75 80 Ala Met Leu ArgLys Gly Ile Cys Glu Tyr His Glu Lys Asn Tyr Ala 85 90 95 Ala Ala Leu GluThr Phe Thr Glu Gly Gln Lys Leu Asp Ser Ala Asp 100 105 110 Ala Asn PheSer Val Trp Ile Lys Arg Cys Gln Glu Ala Gln Asn Gly 115 120 125 Ser GluSer Glu Val Val Ser Pro Lys Phe Ser Phe Phe Met Phe Leu 130 135 140 LeuPhe 145 397 38 PRT Homo sapiens 397 Leu Glu Glu Leu Thr Lys Ala Leu GluGln Lys Pro Asp Asp Ala Gln 1 5 10 15 Tyr Tyr Cys Gln Arg Ala Tyr CysHis Ile Leu Leu Gly Asn Tyr Cys 20 25 30 Val Ala Val Ala Asp Ala 35 39831 PRT Homo sapiens 398 Ala Met Leu Arg Lys Gly Ile Cys Glu Tyr His GluLys Asn Tyr Ala 1 5 10 15 Ala Ala Leu Glu Thr Phe Thr Glu Gly Gln LysLeu Asp Ser Ala 20 25 30 399 37 PRT Homo sapiens 399 Leu Arg Leu Trp AsnArg Asn Gln Met Met His Ser Ile Ile Val Lys 1 5 10 15 Glu Leu Ile ValThr Phe Phe Leu Gly Ile Thr Val Leu Leu Leu Leu 20 25 30 Met Gln Arg SerLeu 35 400 10 PRT Homo sapiens 400 Asn Ser Ile Gln Ile Ile Pro Leu LeuCys 1 5 10 401 228 PRT Homo sapiens 401 Tyr Met His Phe Asn Asn Thr ValAla Lys Leu Thr Cys Lys Asn Leu 1 5 10 15 Ser Leu Ser Thr Tyr Gln AsnGln Ser Ala Ser Gln Trp Thr His Gln 20 25 30 Ser Lys Ile Lys Tyr Asp TrpTyr Gln Thr Glu Ser Gln Val Val Ile 35 40 45 Thr Leu Met Ile Lys Asn ValGln Lys Asn Asp Val Asn Val Glu Phe 50 55 60 Ser Glu Lys Glu Leu Ser AlaLeu Val Lys Leu Pro Ser Gly Glu Asp 65 70 75 80 Tyr Asn Leu Lys Leu GluLeu Leu His Pro Ile Ile Pro Glu Gln Ser 85 90 95 Thr Phe Lys Val Leu SerThr Lys Ile Glu Ile Lys Leu Lys Lys Pro 100 105 110 Glu Ala Val Arg TrpGlu Lys Leu Glu Gly Gln Gly Asp Val Pro Thr 115 120 125 Pro Lys Gln PheVal Ala Asp Val Lys Asn Leu Tyr Pro Ser Ser Ser 130 135 140 Pro Tyr ThrArg Asn Trp Asp Lys Leu Val Gly Glu Ile Lys Glu Glu 145 150 155 160 GluLys Asn Glu Lys Leu Glu Gly Asp Ala Ala Leu Asn Arg Leu Phe 165 170 175Gln Gln Ile Tyr Ser Asp Gly Ser Asp Glu Val Lys Arg Ala Met Asn 180 185190 Lys Ser Phe Met Glu Ser Gly Gly Thr Val Leu Ser Thr Asn Trp Ser 195200 205 Asp Val Gly Lys Arg Lys Val Glu Ile Asn Pro Pro Asp Asp Met Glu210 215 220 Trp Lys Lys Tyr 225 402 29 PRT Homo sapiens 402 Thr Cys LysAsn Leu Ser Leu Ser Thr Tyr Gln Asn Gln Ser Ala Ser 1 5 10 15 Gln TrpThr His Gln Ser Lys Ile Lys Tyr Asp Trp Tyr 20 25 403 24 PRT Homosapiens 403 Glu Lys Glu Leu Ser Ala Leu Val Lys Leu Pro Ser Gly Glu AspTyr 1 5 10 15 Asn Leu Lys Leu Glu Leu Leu His 20 404 29 PRT Homo sapiens404 Leu His Pro Ile Ile Pro Glu Gln Ser Thr Phe Lys Val Leu Ser Thr 1 510 15 Lys Ile Glu Ile Lys Leu Lys Lys Pro Glu Ala Val Arg 20 25 405 24PRT Homo sapiens 405 Lys Gln Phe Val Ala Asp Val Lys Asn Leu Tyr Pro SerSer Ser Pro 1 5 10 15 Tyr Thr Arg Asn Trp Asp Lys Leu 20 406 17 PRT Homosapiens 406 Gly Ser Lys Gly Gln Glu Arg Lys Trp Arg Val Arg Met Gly TyrLeu 1 5 10 15 Asn 407 55 PRT Homo sapiens 407 Gln Arg Tyr Arg Leu LeuPro Leu Phe Cys Tyr Val Cys Ser Arg Lys 1 5 10 15 Ile Lys Leu Asn GluAsn Leu Phe Val Phe Ser Ala Tyr Ser Leu Ala 20 25 30 Thr Leu Pro His ThrTyr Leu Phe Ser Ile Val Glu Cys Ser Ser Phe 35 40 45 Cys Leu Ser Gly ThrArg Asn 50 55 408 27 PRT Homo sapiens 408 Phe Ser Ala Tyr Ser Leu AlaThr Leu Pro His Thr Tyr Leu Phe Ser 1 5 10 15 Ile Val Glu Cys Ser SerPhe Cys Leu Ser Gly 20 25 409 35 PRT Homo sapiens 409 Ala Ser Phe GlySer Cys Ser Leu Ser Leu Pro Cys Ser Ala Arg Glu 1 5 10 15 Arg Thr ProGlu Gly Gly Gly Trp Pro Gly Gly Arg Leu Ser Glu Pro 20 25 30 Leu Pro Ala35 410 7 PRT Homo sapiens 410 Ala Pro Asn Val Val Leu Val 1 5 411 6 PRTHomo sapiens 411 Asp Gly Arg Leu Thr Phe 1 5 412 14 PRT Homo sapiens 412Pro Gly Ser Gln Val Val Lys Leu Pro Phe Ile Asn Phe Met 1 5 10 413 9 PRTHomo sapiens 413 Phe Leu Asn Ala Tyr Thr Asn Ser Pro 1 5 414 36 PRT Homosapiens 414 Ile Cys Cys Pro Ser Arg Ala Ala Met Trp Ser Gly Leu Phe ThrHis 1 5 10 15 Leu Thr Glu Ser Trp Asn Asn Phe Lys Gly Leu Asp Pro AsnTyr Thr 20 25 30 Thr Trp Met Asp 35 415 6 PRT Homo sapiens 415 Thr GlnLys Phe Gly Lys 1 5 416 9 PRT Homo sapiens 416 Asp Tyr Thr Ser Gly HisHis Ser Ile 1 5 417 21 PRT Homo sapiens 417 Ser Asn Arg Val Glu Ala TrpThr Arg Asp Val Ala Phe Leu Leu Arg 1 5 10 15 Gln Glu Gly Arg Pro 20 4188 PRT Homo sapiens 418 Asp Trp Gln Asn Thr Asp Lys Ala 1 5 419 34 PRTHomo sapiens 419 Tyr Leu Gly Leu Asn Leu Pro His Pro Tyr Pro Ser Pro SerSer Gly 1 5 10 15 Glu Asn Phe Gly Ser Ser Thr Phe His Thr Ser Leu TyrTrp Leu Glu 20 25 30 Lys Val 420 8 PRT Homo sapiens 420 Asp Ala Ile LysIle Pro Lys Trp 1 5 421 7 PRT Homo sapiens 421 Tyr Thr Lys Asn Cys ThrGly 1 5 422 25 PRT Homo sapiens 422 Asn Ile Arg Ala Phe Tyr Tyr Ala MetCys Ala Glu Thr Asp Ala Met 1 5 10 15 Leu Gly Glu Ile Ile Leu Ala LeuHis 20 25 423 11 PRT Homo sapiens 423 Leu Asp Leu Leu Gln Lys Thr IleVal Ile Tyr 1 5 10 424 15 PRT Homo sapiens 424 Met Glu His Arg Gln PheTyr Lys Met Ser Met Tyr Glu Ala Ser 1 5 10 15 425 13 PRT Homo sapiens425 His Val Pro Leu Leu Met Met Gly Pro Gly Ile Lys Ala 1 5 10 426 17PRT Homo sapiens 426 Val Val Ser Leu Val Asp Ile Tyr Pro Thr Met Leu AspIle Ala Gly 1 5 10 15 Ile 427 7 PRT Homo sapiens 427 Asp Pro Asp Glu LeuThr Asn 1 5 428 6 PRT Homo sapiens 428 Trp Lys Tyr Ile Ala Tyr 1 5 42982 PRT Homo sapiens 429 Asn Phe Pro Glu Ile Thr Tyr Ser Leu Asp Gln LysLeu His Ser Ile 1 5 10 15 Ile Asn Tyr Pro Lys Val Ser Ala Ser Val HisGln Tyr Asn Lys Glu 20 25 30 Gln Phe Ile Lys Trp Lys Gln Ser Ile Gly GlnAsn Tyr Ser Asn Val 35 40 45 Ile Ala Asn Phe Arg Trp His Gln Asp Trp GlnLys Glu Pro Arg Lys 50 55 60 Tyr Glu Asn Ala Ile Asp Gln Trp Leu Lys ThrHis Met Asn Pro Arg 65 70 75 80 Ala Val 430 12 PRT Homo sapiens 430 PhePro Glu Ile Thr Tyr Ser Leu Asp Gln Lys Leu 1 5 10 431 18 PRT Homosapiens 431 Asn Tyr Pro Lys Val Ser Ala Ser Val His Gln Tyr Asn Lys GluGln 1 5 10 15 Phe Ile 432 9 PRT Homo sapiens 432 Gly Gln Asn Tyr Ser AsnVal Ile Ala 1 5 433 7 PRT Homo sapiens 433 Arg Trp His Gln Asp Trp Gln 15 434 8 PRT Homo sapiens 434 Pro Arg Lys Tyr Glu Asn Ala Ile 1 5 435 35PRT Homo sapiens 435 Arg Asn Ser Leu His Cys Tyr Asn Glu Gln Pro Pro AsnAla Ser Gly 1 5 10 15 Leu Ile Gln Trp Ser Ser Asp Leu Ile Pro Ile SerLeu Gln Cys Gly 20 25 30 Cys Ser Trp 35 436 162 PRT Homo sapiens SITE(1) Xaa equals any of the naturally occurring L-amino acids 436 Xaa LeuTrp Asp Pro Gly Leu Pro Gly Val Cys Arg Cys Gly Ser Ile 1 5 10 15 ValLeu Lys Ser Ala Phe Ser Val Gly Ile Thr Thr Ser Tyr Pro Glu 20 25 30 XaaArg Leu Pro Ile Ile Phe Asn Lys Val Leu Leu Pro Arg Gly Xaa 35 40 45 AlaLeu Gln Pro Cys His Arg Gly Ser Ser Ser Val Leu Ser Gln Gly 50 55 60 IleTyr Tyr Phe Ser Tyr Asp Ile Thr Leu Ala Asn Lys His Leu Ala 65 70 75 80Ile Gly Leu Val His Asn Gly Gln Tyr Arg Ile Lys Thr Phe Asp Ala 85 90 95Asn Thr Gly Asn His Asp Val Ala Ser Gly Ser Thr Val Ile Tyr Leu 100 105110 Gln Pro Glu Asp Glu Val Trp Leu Glu Ile Phe Phe Thr Asp Gln Asn 115120 125 Gly Leu Phe Ser Asp Pro Gly Trp Ala Asp Ser Leu Phe Ser Gly Phe130 135 140 Leu Leu Tyr Val Asp Thr Asp Tyr Leu Asp Ser Ile Ser Glu AspAsp 145 150 155 160 Glu Leu 437 15 PRT Homo sapiens 437 Gly Ser Ile ValLeu Lys Ser Ala Phe Ser Val Gly Ile Thr Thr 1 5 10 15 438 14 PRT Homosapiens 438 Gly Ile Tyr Tyr Phe Ser Tyr Asp Ile Thr Leu Ala Asn Lys 1 510 439 13 PRT Homo sapiens 439 Asp Ser Leu Phe Ser Gly Phe Leu Leu TyrVal Asp Thr 1 5 10 440 13 PRT Homo sapiens 440 Asn His Asp Val Ala SerGly Ser Thr Val Ile Tyr Leu 1 5 10 441 14 PRT Homo sapiens 441 Ser AsnSer His Thr His Thr His Val Lys Ser Phe Leu Arg 1 5 10 442 10 PRT Homosapiens 442 Ile Thr Pro Leu Gly Leu Gly Ala Ala Asp 1 5 10 443 149 PRTHomo sapiens 443 Thr Leu Arg Val Leu Gly Lys Val Pro Ala Val Cys Pro TrpCys Ala 1 5 10 15 Leu Trp Arg Lys Ala Gly Met Asp Met Thr Tyr Ser TrpLeu Ser Arg 20 25 30 Gly Asp Ser Thr Tyr Thr Phe His Glu Gly Pro Val LeuSer Thr Ser 35 40 45 Trp Arg Pro Gly Asp Ser Ala Leu Ser Tyr Thr Cys ArgAla Asn Asn 50 55 60 Pro Ile Ser Asn Val Ser Ser Cys Pro Ile Pro Asp GlyPro Phe Tyr 65 70 75 80 Ala Asp Pro Asn Tyr Ala Ser Glu Lys Pro Ser ThrAla Phe Cys Leu 85 90 95 Leu Ala Lys Gly Leu Leu Ile Phe Leu Leu Leu ValIle Leu Ala Met 100 105 110 Gly Leu Trp Val Ile Arg Val Gln Lys Arg HisLys Met Pro Arg Met 115 120 125 Lys Lys Leu Met Arg Asn Arg Met Lys LeuArg Lys Glu Ala Lys Pro 130 135 140 Gly Ser Ser Pro Ala 145 444 21 PRTHomo sapiens 444 Ala Val Cys Pro Trp Cys Ala Leu Trp Arg Lys Ala Gly MetAsp Met 1 5 10 15 Thr Tyr Ser Trp Leu 20 445 24 PRT Homo sapiens 445 ProGly Asp Ser Ala Leu Ser Tyr Thr Cys Arg Ala Asn Asn Pro Ile 1 5 10 15Ser Asn Val Ser Ser Cys Pro Ile 20 446 24 PRT Homo sapiens 446 Tyr AlaSer Glu Lys Pro Ser Thr Ala Phe Cys Leu Leu Ala Lys Gly 1 5 10 15 LeuLeu Ile Phe Leu Leu Leu Val 20 447 26 PRT Homo sapiens 447 Gln Lys ArgHis Lys Met Pro Arg Met Lys Lys Leu Met Arg Asn Arg 1 5 10 15 Met LysLeu Arg Lys Glu Ala Lys Pro Gly 20 25 448 23 PRT Homo sapiens 448 IleAla Trp Ser Gly Asn Ile Pro Ser Leu Leu Cys Leu Phe Glu His 1 5 10 15Asp Met Ser Phe Gln Asp Glu 20 449 89 PRT Homo sapiens SITE (60) Xaaequals any of the naturally occurring L-amino acids 449 Glu Asn Phe LeuLeu Arg Tyr Lys Gly Pro Ser Asp His Trp Ile Gly 1 5 10 15 Leu Ser ArgGlu Gln Gly Gln Pro Trp Lys Trp Ile Asn Gly Thr Glu 20 25 30 Trp Thr ArgGln Leu Val Met Lys Glu Asp Gly Ala Asn Leu Tyr Val 35 40 45 Ala Lys ValSer Gln Val Pro Arg Met Asn Pro Xaa Leu Ser Trp Val 50 55 60 Leu Leu CysTyr Pro Gly Trp Ser Ala Val Xaa Thr Ile Val Ala His 65 70 75 80 Cys SerLeu Asp Phe Pro Gly Ser Lys 85 450 63 PRT Homo sapiens 450 Glu Leu ThrAla Ile Lys Ser His Gln Tyr Val Leu Gln Ala Ala Cys 1 5 10 15 Pro GluSer Trp Ile Gly Phe Gln Arg Lys Cys Phe Tyr Phe Ser Asp 20 25 30 Asp ThrLys Asn Trp Thr Ser Ser Gln Arg Phe Cys Asp Ser Gln Asp 35 40 45 Ala AspLeu Ala Gln Val Glu Ser Phe Gln Glu Leu Val Arg Lys 50 55 60 451 17 PRTHomo sapiens 451 Trp Ile Gly Leu Ser Arg Glu Gln Gly Gln Pro Trp Lys TrpIle Asn 1 5 10 15 Gly 452 12 PRT Homo sapiens 452 Cys Pro Glu Ser TrpIle Gly Phe Gln Arg Lys Cys 1 5 10 453 16 PRT Homo sapiens 453 Asn PheLeu Leu Arg Tyr Lys Gly Pro Ser Asp His Trp Ile Gly Leu 1 5 10 15 454 50PRT Homo sapiens 454 Ala Ser His Leu Arg Leu Leu Ser Ser Trp Asp Tyr ArgPhe Pro Ile 1 5 10 15 Leu Gly Ala Gly Glu Cys Ala Tyr Leu Asn Asp LysGly Ala Ser Ser 20 25 30 Ala Arg His Tyr Thr Glu Arg Lys Trp Ile Cys SerLys Ser Asp Ile 35 40 45 His Val 50 455 89 PRT Homo sapiens SITE (60)Xaa equals any of the naturally occurring L-amino acids 455 Glu Asn PheLeu Leu Arg Tyr Lys Gly Pro Ser Asp His Trp Ile Gly 1 5 10 15 Leu SerArg Glu Gln Gly Gln Pro Trp Lys Trp Ile Asn Gly Thr Glu 20 25 30 Trp ThrArg Gln Leu Val Met Lys Glu Asp Gly Ala Asn Leu Tyr Val 35 40 45 Ala LysVal Ser Gln Val Pro Arg Met Asn Pro Xaa Leu Ser Trp Val 50 55 60 Leu LeuCys Tyr Pro Gly Trp Ser Ala Val Xaa Thr Ile Val Ala His 65 70 75 80 CysSer Leu Asp Phe Pro Gly Ser Lys 85 456 76 PRT Homo sapiens SITE (9) Xaaequals any of the naturally occurring L-amino acids 456 Ser Trp Thr SerSer Leu Leu Asn Xaa Cys Leu His Ser Lys Glu His 1 5 10 15 Ser Ile LysAla Thr Xaa Ile Trp Arg Leu Phe Phe Xaa Ile Leu Thr 20 25 30 Ile Ile LeuCys Gly Met Val Ala Ala Leu Ser Ala Ile Arg Ala Asn 35 40 45 Cys His GlnGlu Pro Ser Val Cys Ser Ser Ser Cys Met Pro Arg Lys 50 55 60 Leu Asp TrpPhe Ser Lys Lys Val Phe Leu Phe Phe 65 70 75 457 39 PRT Homo sapiens 457Glu Gln Leu Glu Glu Leu Glu Leu Lys Lys Lys Asp Phe Ile Lys Ile 1 5 1015 Leu Glu Ser Val Gln Gly Asn Trp Arg Gln Asn Glu Asp Ser Gly Lys 20 2530 Gly Pro Gln Arg Ser Cys Leu 35 458 19 PRT Homo sapiens 458 Phe TrpPro Glu Ser Lys Ile Gln Pro Tyr Lys Asp Met Phe Ser Cys 1 5 10 15 GluIle Ile 459 58 PRT Homo sapiens 459 Glu Gln Leu Glu Glu Leu Glu Leu LysLys Lys Asp Phe Ile Lys Ile 1 5 10 15 Leu Glu Ser Val Gln Gly Asn TrpArg Gln Asn Glu Asp Ser Gly Lys 20 25 30 Gly Pro Gln Arg Ser Cys Leu HisSer Lys Glu His Ser Ile Lys Ala 35 40 45 Thr Leu Ile Trp Arg Leu Phe PheLeu Ile 50 55 460 36 PRT Homo sapiens SITE (18) Xaa equals any of thenaturally occurring L-amino acids 460 Glu Asn Phe Leu Leu Arg Tyr LysGly Pro Ser Asp His Trp Ile Gly 1 5 10 15 Leu Xaa Xaa Glu Gln Gly GlnPro Trp Lys Trp Ile Asn Gly Thr Glu 20 25 30 Trp Thr Arg Gln 35 461 7PRT Homo sapiens 461 Arg His Glu Pro Asp Pro Met 1 5 462 109 PRT Homosapiens SITE (24) Xaa equals any of the naturally occurring L-aminoacids 462 Leu Lys Gly Arg Glu Ala Gly Ala Gly Pro Gly Thr Ala Gly AlaPro 1 5 10 15 Gly Arg Glu Asp Ala Asn Gly Xaa Xaa Arg Gly Arg Gly GlyXaa His 20 25 30 Gln Leu Tyr Leu Trp Val Asp Asn Ile Pro Leu Ser Arg ProLys Arg 35 40 45 Asn Leu Ser Arg Asp Phe Ser Asp Gly Val Leu Val Ala GluVal Ile 50 55 60 Lys Phe Tyr Phe Pro Lys Met Val Glu Met His Asn Tyr ValGly Thr 65 70 75 80 Ser Ser Leu Gln Gln Lys Leu Ser Asn Trp Gly His LeuAsn Arg Lys 85 90 95 Val Leu Lys Arg Leu Asn Phe Ser Val Pro Asp Asp Val100 105 463 25 PRT Homo sapiens 463 Trp Val Asp Asn Ile Pro Leu Ser ArgPro Lys Arg Asn Leu Ser Arg 1 5 10 15 Asp Phe Ser Asp Gly Val Leu ValAla 20 25 464 25 PRT Homo sapiens 464 Tyr Val Gly Thr Ser Ser Leu GlnGln Lys Leu Ser Asn Trp Gly His 1 5 10 15 Leu Asn Arg Lys Val Leu LysArg Leu 20 25 465 97 PRT Homo sapiens 465 Gly Ser Ala Trp Arg Arg GlyArg Gly Ala Gly Ser Arg Ala Pro Ala 1 5 10 15 Pro Tyr Arg Ser Trp LeuPro Arg Met Ala Val Ala Thr Trp Met Trp 20 25 30 Val Tyr Pro Arg Arg ProGlu Val Lys Val Ser Arg Thr Pro Arg Glu 35 40 45 Gly Val Ser Ser Ala GlyThr Gly Arg Arg Arg Leu Gly Leu Gln Arg 50 55 60 Ile Thr Gly Arg Cys ArgAla Thr Pro Ala Ser Ser Ser Arg Ser Leu 65 70 75 80 Lys Arg Ser Arg SerCys Trp Pro Leu Lys Arg Pro Cys Arg Ser Cys 85 90 95 Arg 466 21 PRT Homosapiens 466 Trp Leu Pro Arg Met Ala Val Ala Thr Trp Met Trp Val Tyr ProArg 1 5 10 15 Arg Pro Glu Val Lys 20 467 23 PRT Homo sapiens 467 Cys ArgAla Thr Pro Ala Ser Ser Ser Arg Ser Leu Lys Arg Ser Arg 1 5 10 15 SerCys Trp Pro Leu Lys Arg 20 468 347 PRT Homo sapiens SITE (241) Xaaequals any of the naturally occurring L-amino acids 468 Glu His Asn ThrAsp Phe Asn Gly Ala Ala Leu Ser Arg Asn Leu Gln 1 5 10 15 Thr Phe ArgLeu Ser Thr Pro Cys Ala Arg Arg Glu Gly Arg Leu Leu 20 25 30 Arg Ala HisArg Arg Cys Pro Pro Tyr Ser Trp Arg Ser His Ala Ser 35 40 45 Pro Leu ProLeu Gln Leu Leu Arg Ser Pro Ser Pro Arg Trp Val Pro 50 55 60 Gly Lys LeuPro Gly Gly Ala Gly Glu Pro Leu Ser Gly Pro Gly Gln 65 70 75 80 Ile ProPro Trp Leu Arg Ala Trp Gly Thr Ser Leu Asp Gly Asp Ala 85 90 95 Ala ValLeu Gly Ala Gly Arg Gly Pro Asp Ser Gly Gly Val Asp Arg 100 105 110 AlaLys Gly Pro Pro Pro Lys Ala Gln Arg Arg Glu Met Gln Gly Arg 115 120 125Ala Gln Gly Val Gly His Cys Phe Gly Gly Gln Ala Arg Ser Leu His 130 135140 Val Ala Ser Gly Leu Trp Lys Ala Val His Ser Pro Asp Pro Asp Leu 145150 155 160 Arg Ser Gly Arg Arg Arg Leu Ser Pro Gly Pro Ala Leu Leu GluPhe 165 170 175 Leu Ser His Leu Leu His Ala His Pro Ser Gln Gly Arg ArgAla Leu 180 185 190 Gly Pro Gln Gln Ala Arg Glu Ser Ser Gly Leu Arg ProPro Asn Gly 195 200 205 Leu Ser Ile Gly Gly Trp Val Arg Arg Gly Val GlyAla Leu Ala Gly 210 215 220 Thr Arg Ala Ser Pro Arg Gly Pro Gly Arg ArgSer Pro Leu Leu Thr 225 230 235 240 Xaa Arg Xaa Leu Glu Pro Pro Gly GluVal Phe Asp Pro His Ile Leu 245 250 255 Glu Leu Glu Gln Val Leu Gln AlaPro Tyr Leu His Leu Gln Asp Leu 260 265 270 His Gly Leu Leu Arg Gly GlnGln Leu Leu Leu Leu Phe Ser Asp Leu 275 280 285 Glu Asp Glu Ala Gly ValAla Leu Gln Arg Pro Val Ile Arg Trp Arg 290 295 300 Pro Arg Arg Arg ArgPro Val Pro Ala Glu Leu Thr Pro Ser Leu Gly 305 310 315 320 Val Arg AspThr Phe Thr Ser Gly Leu Leu Gly Tyr Thr His Ile His 325 330 335 Val AlaThr Ala Ile Leu Gly Ser Gln Leu Leu 340 345 469 26 PRT Homo sapiens 469Thr Asp Phe Asn Gly Ala Ala Leu Ser Arg Asn Leu Gln Thr Phe Arg 1 5 1015 Leu Ser Thr Pro Cys Ala Arg Arg Glu Gly 20 25 470 25 PRT Homo sapiens470 Arg Cys Pro Pro Tyr Ser Trp Arg Ser His Ala Ser Pro Leu Pro Leu 1 510 15 Gln Leu Leu Arg Ser Pro Ser Pro Arg 20 25 471 24 PRT Homo sapiens471 Gly Ala Gly Glu Pro Leu Ser Gly Pro Gly Gln Ile Pro Pro Trp Leu 1 510 15 Arg Ala Trp Gly Thr Ser Leu Asp 20 472 30 PRT Homo sapiens 472 LeuGly Ala Gly Arg Gly Pro Asp Ser Gly Gly Val Asp Arg Ala Lys 1 5 10 15Gly Pro Pro Pro Lys Ala Gln Arg Arg Glu Met Gln Gly Arg 20 25 30 473 23PRT Homo sapiens 473 Gln Ala Arg Ser Leu His Val Ala Ser Gly Leu Trp LysAla Val His 1 5 10 15 Ser Pro Asp Pro Asp Leu Arg 20 474 20 PRT Homosapiens 474 His Pro Ser Gln Gly Arg Arg Ala Leu Gly Pro Gln Gln Ala ArgGlu 1 5 10 15 Ser Ser Gly Leu 20 475 27 PRT Homo sapiens 475 Ile Gly GlyTrp Val Arg Arg Gly Val Gly Ala Leu Ala Gly Thr Arg 1 5 10 15 Ala SerPro Arg Gly Pro Gly Arg Arg Ser Pro 20 25 476 25 PRT Homo sapiens 476Glu Pro Pro Gly Glu Val Phe Asp Pro His Ile Leu Glu Leu Glu Gln 1 5 1015 Val Leu Gln Ala Pro Tyr Leu His Leu 20 25 477 28 PRT Homo sapiens 477Val Pro Ala Glu Leu Thr Pro Ser Leu Gly Val Arg Asp Thr Phe Thr 1 5 1015 Ser Gly Leu Leu Gly Tyr Thr His Ile His Val Ala 20 25 478 187 PRTHomo sapiens 478 Ala Lys Asn Ser Gln Lys Glu Glu Asn Pro Glu His Val GluIle Gln 1 5 10 15 Lys Met Met Asp Ser Leu Phe Leu Lys Leu Asp Ala LeuSer Asn Phe 20 25 30 His Phe Ile Pro Lys Pro Pro Val Pro Glu Ile Lys ValVal Ser Asn 35 40 45 Leu Pro Ala Ile Thr Met Glu Glu Val Ala Pro Val SerVal Ser Asp 50 55 60 Ala Ala Leu Leu Ala Pro Glu Glu Ile Lys Glu Lys AsnLys Ala Gly 65 70 75 80 Asp Ile Lys Thr Ala Ala Glu Lys Thr Ala Thr AspLys Lys Arg Glu 85 90 95 Arg Arg Lys Lys Lys Tyr Gln Lys Arg Met Lys IleLys Glu Lys Glu 100 105 110 Lys Arg Arg Lys Leu Leu Glu Lys Ser Ser ValAsp Gln Ala Gly Lys 115 120 125 Tyr Ser Lys Thr Val Ala Ser Glu Lys LeuLys Gln Leu Thr Lys Thr 130 135 140 Gly Lys Ala Ser Phe Ile Lys Val ArgThr Arg Glu Arg Lys Leu Leu 145 150 155 160 Lys Gly Thr Phe Val Gly GluVal Asp Ser Lys Cys Trp Val Thr Gly 165 170 175 Met Ser Glu Pro Ala AspSer Pro Pro Val Gly 180 185 479 51 PRT Homo sapiens 479 Leu Gln Asp GluGly Lys Asp Lys Ala Leu Lys Ser Ser Gln Ala Phe 1 5 10 15 Phe Ser LysLeu Gln Asp Gln Val Lys Met Gln Ile Asn Asp Ala Lys 20 25 30 Lys Thr GluLys Lys Lys Lys Lys Arg Gln Asp Ile Ser Val His Lys 35 40 45 Leu Lys Leu50 480 29 PRT Homo sapiens 480 Asp Glu Gly Lys Asp Lys Ala Leu Lys SerSer Gln Ala Phe Phe Ser 1 5 10 15 Lys Leu Gln Asp Gln Val Lys Met GlnIle Asn Asp Ala 20 25 481 28 PRT Homo sapiens 481 Glu Glu Asn Pro GluHis Val Glu Ile Gln Lys Met Met Asp Ser Leu 1 5 10 15 Phe Leu Lys LeuAsp Ala Leu Ser Asn Phe His Phe 20 25 482 13 PRT Homo sapiens 482 SerAsn Leu Pro Ala Ile Thr Met Glu Glu Val Ala Pro 1 5 10 483 31 PRT Homosapiens 483 Ser Ser Val Asp Gln Ala Gly Lys Tyr Ser Lys Thr Val Ala SerGlu 1 5 10 15 Lys Leu Lys Gln Leu Thr Lys Thr Gly Lys Ala Ser Phe IleLys 20 25 30 484 23 PRT Homo sapiens 484 Val Ser Val Ser Asp Ala Ala LeuLeu Ala Pro Glu Glu Ile Lys Glu 1 5 10 15 Lys Asn Lys Ala Gly Asp Ile 20485 11 PRT Homo sapiens 485 Val Leu Glu Val Met Val Thr Val Ala Pro Lys1 5 10 486 35 PRT Homo sapiens 486 Leu Gln Asp Glu Gly Lys Asp Lys AlaLeu Lys Ser Ser Gln Ala Phe 1 5 10 15 Phe Ser Lys Leu Gln Asp Gln ValLys Met Gln Ile Asn Asp Ala Lys 20 25 30 Lys Thr Glu 35 487 34 PRT Homosapiens 487 His Glu Ala Ala Gln Gly Ala Val Cys Arg Gly Gln Gly Ala ProAla 1 5 10 15 Thr Asn Pro Gln Ala Pro Val Ala Ala Ala Ala Arg Val AlaArg Arg 20 25 30 Val Asn 488 255 PRT Homo sapiens 488 Lys Ile Pro SerAla Asn Arg Arg Ala Thr Arg Cys Leu Gly Cys Asp 1 5 10 15 His Gln AsnPhe Val Lys Val Arg Asn Lys His Lys Gly Lys Pro Thr 20 25 30 Phe Met GluGlu Val Leu Glu His Leu Pro Gly Lys Thr Gln Asp Glu 35 40 45 Val Gln GlnHis Glu Lys Trp Tyr Gln Lys Phe Leu Ala Leu Glu Glu 50 55 60 Arg Lys LysGlu Ser Ile Gln Ile Trp Lys Thr Lys Lys Gln Gln Lys 65 70 75 80 Arg GluGlu Ile Phe Lys Leu Lys Glu Lys Ala Asp Asn Thr Pro Val 85 90 95 Leu PheHis Asn Lys Gln Glu Asp Asn Gln Lys Gln Lys Glu Glu Gln 100 105 110 ArgLys Lys Gln Lys Leu Ala Val Glu Ala Trp Lys Lys Gln Lys Ser 115 120 125Ile Glu Met Ser Met Lys Cys Ala Ser Gln Leu Lys Lys Lys Lys Lys 130 135140 Lys Lys Lys Lys Asn Gln Lys Glu Arg Gln Arg Gln Phe Lys Leu Lys 145150 155 160 Leu Leu Leu Glu Ser Tyr Thr Gln Gln Lys Lys Glu Gln Glu GluPhe 165 170 175 Leu Arg Leu Glu Lys Glu Ile Arg Glu Lys Ala Glu Lys AlaGlu Lys 180 185 190 Arg Lys Asn Ala Ala Asp Glu Ile Ser Arg Phe Gln GluArg Asp Leu 195 200 205 His Lys Leu Glu Leu Lys Ile Leu Asp Arg Gln AlaLys Glu Asp Glu 210 215 220 Lys Ser Gln Lys Gln Arg Arg Leu Ala Lys LeuLys Glu Lys Val Glu 225 230 235 240 Asn Asn Val Ser Arg Asp Pro Ser ArgLeu Tyr Lys Pro Thr Lys 245 250 255 489 24 PRT Homo sapiens 489 Val LysVal Arg Asn Lys His Lys Gly Lys Pro Thr Phe Met Glu Glu 1 5 10 15 ValLeu Glu His Leu Pro Gly Lys 20 490 23 PRT Homo sapiens 490 Gln His GluLys Trp Tyr Gln Lys Phe Leu Ala Leu Glu Glu Arg Lys 1 5 10 15 Lys GluSer Ile Gln Ile Trp 20 491 31 PRT Homo sapiens 491 Phe Lys Leu Lys GluLys Ala Asp Asn Thr Pro Val Leu Phe His Asn 1 5 10 15 Lys Gln Glu AspAsn Gln Lys Gln Lys Glu Glu Gln Arg Lys Lys 20 25 30 492 36 PRT Homosapiens 492 Phe Leu Arg Leu Glu Lys Glu Ile Arg Glu Lys Ala Glu Lys AlaGlu 1 5 10 15 Lys Arg Lys Asn Ala Ala Asp Glu Ile Ser Arg Phe Gln GluArg Asp 20 25 30 Leu His Lys Leu 35 493 24 PRT Homo sapiens 493 Lys GlnArg Arg Leu Ala Lys Leu Lys Glu Lys Val Glu Asn Asn Val 1 5 10 15 SerArg Asp Pro Ser Arg Leu Tyr 20 494 18 PRT Homo sapiens 494 Val Lys ProPro Asp Gln Ser Cys Asn His Trp Arg Asp Glu Gln Cys 1 5 10 15 Leu Val495 20 PRT Homo sapiens 495 Met Ala Ile Pro Ala Phe Ser Ser Cys Gln GlnIle Ser Ser Ala Ala 1 5 10 15 Ala Leu Gln Ile 20 496 14 PRT Homo sapiens496 Cys Asn Gly Pro Phe Lys His Phe Ser Phe Thr Val Ser Thr 1 5 10 49718 PRT Homo sapiens 497 Ile Arg His Glu Arg Leu Trp Ala Glu Leu Ala LeuLeu Thr Gly Arg 1 5 10 15 Asn Glu 498 59 PRT Homo sapiens 498 Gly ThrGlu Ser Pro Met Val Met Cys Cys Arg Glu Val Ser Gln Ser 1 5 10 15 GluAsn Cys Leu Phe Leu Asp Thr Thr Phe Arg Phe Ile Phe Gly Lys 20 25 30 ThrPhe Thr Asn His Asp Tyr Ile Ser Ile His Phe Tyr Phe Leu Lys 35 40 45 AlaPhe Leu Phe Ser Phe Phe Tyr Ser Asn Val 50 55 499 15 PRT Homo sapiens499 Ile Arg His Glu Glu Lys Gly Gly Lys Ala Gln Arg Trp Ala Glu 1 5 1015 500 11 PRT Homo sapiens 500 Cys Arg Trp Arg Pro Glu Ser Ala Ala ProCys 1 5 10 501 12 PRT Homo sapiens 501 Thr Arg Pro Gly Arg Gly Ala GlnAla Pro Val Lys 1 5 10 502 21 PRT Homo sapiens 502 Met Val Ser Trp MetIle Ser Arg Ala Val Val Leu Val Phe Gly Met 1 5 10 15 Leu Tyr Pro AlaTyr 20 503 17 PRT Homo sapiens 503 Gly Met Leu Tyr Pro Ala Tyr Tyr SerTyr Lys Ala Val Lys Thr Lys 1 5 10 15 Asn 504 17 PRT Homo sapiens 504Glu Tyr Val Arg Trp Met Met Tyr Trp Ile Val Phe Ala Leu Tyr Thr 1 5 1015 Val 505 17 PRT Homo sapiens 505 Tyr Pro Ala Tyr Tyr Ser Tyr Lys AlaVal Lys Thr Lys Asn Val Lys 1 5 10 15 Glu 506 13 PRT Homo sapiens 506Val Ala Trp Phe Pro Leu Tyr Tyr Glu Leu Lys Ile Ala 1 5 10 507 186 PRTHomo sapiens SITE (181) Xaa equals any of the naturally occurringL-amino acids 507 Met Val Ser Trp Met Ile Ser Arg Ala Val Val Leu ValPhe Gly Met 1 5 10 15 Leu Tyr Pro Ala Tyr Tyr Ser Tyr Lys Ala Val LysThr Lys Asn Val 20 25 30 Lys Glu Tyr Val Arg Trp Met Met Tyr Trp Ile ValPhe Ala Leu Tyr 35 40 45 Thr Val Ile Glu Thr Val Ala Asp Gln Thr Val AlaTrp Phe Pro Leu 50 55 60 Tyr Tyr Glu Leu Lys Ile Ala Phe Val Ile Trp LeuLeu Ser Pro Tyr 65 70 75 80 Thr Lys Gly Ala Ser Leu Ile Tyr Arg Lys PheLeu His Pro Leu Leu 85 90 95 Ser Ser Lys Glu Arg Glu Ile Asp Asp Tyr IleVal Gln Ala Lys Glu 100 105 110 Arg Gly Tyr Glu Thr Met Val Asn Phe GlyArg Gln Gly Leu Asn Leu 115 120 125 Ala Ala Thr Ala Ala Val Thr Ala AlaVal Lys Ser Gln Gly Ala Ile 130 135 140 Thr Glu Arg Leu Arg Ser Phe SerMet His Asp Leu Thr Thr Ile Gln 145 150 155 160 Gly Asp Glu Pro Val GlyGln Arg Pro Tyr Gln Pro Leu Pro Glu Ala 165 170 175 Lys Lys Lys Ser XaaGln Pro Pro Val Asn 180 185 508 15 PRT Homo sapiens 508 Gln Pro Tyr GlnVal Leu Pro Ser Arg Gln Val Phe Ala Leu Ile 1 5 10 15 509 24 PRT Homosapiens 509 Val Phe Ser Cys Ile Tyr Gly Glu Gly Tyr Ser Asn Ala His GluSer 1 5 10 15 Lys Gln Met Tyr Cys Val Phe Asn 20 510 18 PRT Homo sapiens510 Arg Asn Glu Asp Ala Cys Arg Tyr Gly Ser Ala Ile Gly Val Leu Ala 1 510 15 Phe Leu 511 17 PRT Homo sapiens 511 Leu Val Val Asp Ala Tyr PhePro Gln Ile Ser Asn Ala Thr Asp Arg 1 5 10 15 Lys 512 25 PRT Homosapiens 512 Ser Ala Leu Trp Thr Phe Leu Trp Phe Val Gly Phe Cys Phe LeuThr 1 5 10 15 Asn Gln Trp Ala Val Thr Asn Pro Lys 20 25 513 82 PRT Homosapiens 513 Leu Asn Ile Asp Ser Phe Asp Tyr Gly Lys Phe Glu Ser Leu LeuAla 1 5 10 15 Lys Gln His Tyr Lys Phe Ser Phe Leu Leu Pro Leu Ala AlaGly Thr 20 25 30 Glu Arg Cys Lys Trp Trp Leu Lys Ile Glu Glu Ala Ser SerAsp Gln 35 40 45 Cys Gly Cys Trp Phe Leu Val Lys Cys Val Pro Lys Pro ProSer Pro 50 55 60 Cys Arg Gln Pro Pro Thr Gln Val Ser Lys Ile Gly His AlaPro Phe 65 70 75 80 Phe Leu 514 13 PRT Homo sapiens 514 Ser Leu Gln TyrArg Ile Arg Ile Pro Gly Arg Pro Thr 1 5 10 515 22 PRT Homo sapiens 515Asp Leu Val Thr Tyr Thr Ser Ser Leu Gln Tyr Arg Ile Arg Ile Pro 1 5 1015 Gly Arg Pro Thr Arg Pro 20 516 36 PRT Homo sapiens 516 Leu Gly AsnLys Lys Tyr Ile Asn Ile Arg Cys Leu Glu Met Gln Val 1 5 10 15 Thr LeuLys Ile Leu Cys Glu Ile Glu Lys Lys Glu Arg Arg Gly Thr 20 25 30 His CysLeu Val 35 517 22 PRT Homo sapiens 517 Val Lys Thr Ala Glu Cys Tyr SerIle Pro Leu Gly Ser Cys Pro Val 1 5 10 15 Asn Ile Gln Arg Val Arg 20 51860 PRT Homo sapiens 518 Leu Phe Tyr Leu Leu Thr Cys Ser Cys Ala Pro GlyHis Leu Ala Phe 1 5 10 15 Val Cys Ser Gln Cys Leu Pro Phe Asp Met GlyLys Glu Leu Trp Pro 20 25 30 Lys Ser Pro Ser Ser Cys Thr Ser Thr Ser ValAla Gln Gly Trp Gly 35 40 45 Gly Arg Gly Arg Pro Ser Pro Tyr Ile Cys ValVal 50 55 60 519 61 PRT Homo sapiens 519 Ile Gln Gly Ser Arg Leu Pro ProLeu Pro Ala Pro Leu His Pro Leu 1 5 10 15 Pro Leu Ile Tyr Leu Leu LeuGly Ser Pro Ala Gln Ser Trp Leu Leu 20 25 30 Val Pro Ser Trp Gly His ProSer Thr Leu Thr Leu Thr Met Ala Ala 35 40 45 Glu His Gln Ala Trp Pro SerGly Phe His Gly Asp His 50 55 60 520 23 PRT Homo sapiens 520 Val Asp ProPro Gly Cys Arg Asn Ser Ala Arg Gly Cys Thr Arg Leu 1 5 10 15 Leu ArgGly Ser Ser Lys Ile 20 521 12 PRT Homo sapiens 521 Ile Thr Leu Cys LeuVal Cys Ile Val Ala Asn Ala 1 5 10 522 24 PRT Homo sapiens 522 Val ThrAla Tyr Gln Asn Gln Gln Ile Thr Arg Leu Lys Ile Asp Arg 1 5 10 15 AsnPro Phe Ala Lys Gly Phe Arg 20 523 16 PRT Homo sapiens 523 Gly Thr AlaThr Val Thr Ala Tyr Gln Asn Gln Gln Ile Thr Arg Leu 1 5 10 15 524 24 PRTHomo sapiens 524 Lys Ile Asp Arg Asn Pro Phe Ala Lys Gly Phe Arg Asp SerGly Arg 1 5 10 15 Asn Arg Met Gly Leu Glu Ala Leu 20 525 21 PRT Homosapiens 525 Ser Thr Leu Leu Gln Val Leu Gly Met Ala Phe Leu Pro Leu ThrLeu 1 5 10 15 Thr Phe Cys Leu Ala 20 526 30 PRT Homo sapiens 526 Val GluSer Tyr Ala Phe Trp Arg Pro Ser Leu Arg Thr Leu Thr Phe 1 5 10 15 GluAsp Ile Pro Gly Ile Pro Lys Gln Gly Asn Ala Ser Ser 20 25 30 527 14 PRTHomo sapiens 527 Gln Ala Gln Ser Asp Cys Ser Cys Ser Thr Val Ser Pro Gly1 5 10 528 24 PRT Homo sapiens 528 Val Leu Ala Gly Ile Val Met Gly AspLeu Val Leu Thr Val Leu Ile 1 5 10 15 Ala Leu Ala Val Tyr Phe Leu Gly 20529 37 PRT Homo sapiens 529 Val Pro Arg Gly Arg Gly Ala Ala Glu Ala ThrArg Lys Gln Arg Ile 1 5 10 15 Thr Glu Thr Glu Ser Pro Tyr Gln Glu LeuGln Gly Gln Arg Ser Asp 20 25 30 Val Tyr Ser Asp Leu 35 530 22 PRT Homosapiens 530 Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser AspVal 1 5 10 15 Tyr Ser Asp Leu Asn Thr 20 531 28 PRT Homo sapiens 531 PheLeu Cys Ala Leu Ser Pro Leu Gly Gln Leu Leu Gln Asp Arg Tyr 1 5 10 15Gly Trp Arg Gly Gly Phe Leu Ile Leu Gly Gly Leu 20 25 532 27 PRT Homosapiens SITE (22) Xaa equals any of the naturally occurring L-aminoacids 532 Leu Leu Asn Cys Cys Val Cys Ala Ala Leu Met Arg Pro Leu ValVal 1 5 10 15 Thr Ala Gln Pro Gly Xaa Gly Pro Pro Arg Pro 20 25 533 25PRT Homo sapiens SITE (5) Xaa equals any of the naturally occurringL-amino acids 533 Ser Arg Arg Leu Xaa Asp Leu Ser Val Phe Arg Asp ArgGly Phe Val 1 5 10 15 Leu Tyr Ala Val Ala Ala Ser Val Met 20 25 534 57PRT Homo sapiens 534 Met Met Ala Thr Pro Ser Thr Arg Pro Pro Pro Pro AlaAla Ser Thr 1 5 10 15 Thr Ser Ala Thr Ala Pro Ala Leu Pro Pro Arg ProPro Trp Pro Trp 20 25 30 Pro Pro Ser Ser Trp Pro Pro Ser Gly Val Ser SerLys Ala Pro Glu 35 40 45 Ala Asp Pro Leu Lys Asn Lys Ala Leu 50 55 53576 PRT Homo sapiens 535 Leu Leu Leu Thr Ser Pro Leu Pro Arg Cys Pro ProAla Cys Ser His 1 5 10 15 Asp Ala Pro Ala His Pro Asp Pro Gly Gly ProHis Gly Leu Thr Ser 20 25 30 Gly Pro Gly Leu Gly Leu Pro Arg Val Cys LeuGln Arg Arg Gln Leu 35 40 45 Leu Gln Pro His Ala Leu Pro Gly Tyr Gly CysLeu Leu His Asp His 50 55 60 Ala His Leu Leu His Pro His Gln Asp Glu GlyGln 65 70 75 536 56 PRT Homo sapiens 536 Trp Leu Leu Gln Ala Arg Val HisHis Leu Leu Leu Pro Val Arg Pro 1 5 10 15 Leu Gln Arg His Arg Pro CysHis Pro Gly His Pro Gly Pro Gly Pro 20 25 30 His Pro Pro Gly His Pro LeuGly Ser Pro Leu Lys Pro Pro Arg Gln 35 40 45 Thr His Ser Arg Thr Lys LeuSer 50 55 537 52 PRT Homo sapiens 537 Gln Glu Phe Gln Thr Gly Leu GlyAsn Met Val Lys Pro Cys Leu Tyr 1 5 10 15 Glu Lys Tyr Arg Asn Ile SerTrp Leu Trp Trp His Thr Pro Val Val 20 25 30 Pro Ala Thr Trp Glu Ala GluVal Gly Gly Ser Leu Glu Pro Gly Arg 35 40 45 Leu Arg Leu Gln 50 538 65PRT Homo sapiens 538 Ile Leu Gly Gly Glu Ser Ile Leu Ile Leu Ser Trp ValPhe Ser Tyr 1 5 10 15 Ile Phe Phe Arg Ile Ala Leu Glu Ile Thr Ile TyrIle Leu Asn Val 20 25 30 Ser Pro Phe Cys Leu Gly Arg Trp Leu Met Pro ValIle Pro Ala Leu 35 40 45 Trp Glu Ala Glu Val Gly Gly Leu Pro Glu Leu ArgSer Ser Arg Pro 50 55 60 Ala 65 539 15 PRT Homo sapiens 539 Met Pro LysGln Leu Ala Gln Leu Leu Tyr Arg Leu Pro Arg Gly 1 5 10 15 540 46 PRTHomo sapiens 540 Leu Phe Gln Ala Ile Ser Val Ser Gly Ser His Arg Gln GlySer Arg 1 5 10 15 Thr Trp Asn Thr Leu Thr Glu Gly Asn Ala Glu Ala AlaCys Thr Val 20 25 30 Ala Leu Gln Thr Ser Lys Arg Leu Ile Leu Ala Ser ArgTrp 35 40 45 541 50 PRT Homo sapiens 541 Thr Leu Ser Phe Met Asn Ser HisCys Val Pro Ile Lys Ala Leu Phe 1 5 10 15 Phe Leu Ser Val Val Ser TyrIle Phe Ile Met Pro His His Ile Phe 20 25 30 Phe Thr Val Lys Ile Leu LysSer Cys Phe Gln Val Gly Gln Leu Met 35 40 45 Lys Leu 50 542 109 PRT Homosapiens 542 Arg Pro Thr Arg Pro Ile Thr Phe Ser Ser Asn Ile Ser Glu TrpVal 1 5 10 15 Pro Ser Thr Gly Phe Gln Asp Leu Glu His Phe Asn Arg ArgLys Cys 20 25 30 Arg Ser Ser Leu His Ser Cys Phe Thr Asp Phe Gln Glu AlaAsp Ser 35 40 45 Gly Phe Lys Met Glu Pro Trp Ser Trp Phe Phe Phe Phe PhePhe Phe 50 55 60 Phe Pro Gln Arg Thr Cys Gly Cys Ala Leu Cys Val Leu PheLeu Phe 65 70 75 80 Ser Ile Trp Gly Pro His Gly Lys Glu Leu Leu Asn SerPhe Leu Tyr 85 90 95 Glu Leu Pro Leu Cys Ser Tyr Lys Gly Pro Phe Leu Ser100 105 543 62 PRT Homo sapiens 543 Val Asp Pro Arg Val Arg Leu Pro LeuPhe Trp Trp Gln Pro Ser Cys 1 5 10 15 Ala Val Tyr Leu Phe Pro Arg ValTyr Asn Asn Met Cys Thr Arg Val 20 25 30 Leu Gly Thr Leu Pro His Cys TrpAsp Leu Ala Thr Leu Leu Gln Pro 35 40 45 Ser Ser Arg Ile Trp Gly Asn ValSer Glu Ala Pro Gly Met 50 55 60 544 87 PRT Homo sapiens 544 Val Pro TyrHis Ile Ala Gly Thr Leu Pro His Cys Cys Ser Leu Pro 1 5 10 15 Val GlyTyr Gly Gly Met Ser Val Arg Leu Gln Gly Cys Arg Tyr Val 20 25 30 Gly AsnVal Gly Pro Gln Gly Asn Met Gln Ser Gly Arg Ser Trp Ala 35 40 45 Leu LysMet Val Leu Leu Cys Asn Ser Cys Leu Gly Leu Gly Val Gly 50 55 60 Ser ValGly Pro Ser Met Ser Ser Leu Phe Gly Ala Val Leu Ser Glu 65 70 75 80 ThrPro Gly Ser Ser Val Tyr 85 545 29 PRT Homo sapiens 545 Met Leu Asp ProArg Ala Thr Cys Asn Leu Val Gly Val Gly Leu Ser 1 5 10 15 Lys Trp CysCys Cys Val Thr Ala Ala Trp Val Leu Gly 20 25 546 65 PRT Homo sapiensSITE (48) Xaa equals any of the naturally occurring L-amino acids 546His Gly Asp Trp Ile Tyr Val His Ile Val Glu Gln Leu Asn Gln Ala 1 5 1015 Asn Asn Lys Ser Val Thr Ser His Thr Tyr Phe Val Val Lys Thr Cys 20 2530 Lys Ile His Ser Leu Ser Asn Phe Gln Ala Ser Asn Thr Leu Leu Xaa 35 4045 Thr Val Val Thr Met Leu Tyr Asn Arg Ser Leu Glu Leu Ile Leu Pro 50 5560 Val 65 547 68 PRT Homo sapiens SITE (26) Xaa equals any of thenaturally occurring L-amino acids 547 Thr Tyr Ser Ser Cys Leu Thr LysIle Leu Tyr Ser Leu Ile Asn Ile 1 5 10 15 Tyr Pro Ile Pro His Cys SerPro Ala Xaa Ile Thr Thr Ile Leu Leu 20 25 30 Ser Ala Ser Met Asn Leu ThrPhe Phe Phe Phe Arg Phe His Ile Cys 35 40 45 Glu Ile Ala Gln Tyr Leu SerPhe Cys Ala Trp Leu Ile Ser Leu Asn 50 55 60 Ile Lys Ser Leu 65 548 33PRT Homo sapiens 548 Met Asn Leu Thr Phe Phe Phe Phe Arg Phe His Ile CysGlu Ile Ala 1 5 10 15 Gln Tyr Leu Ser Phe Cys Ala Trp Leu Ile Ser LeuAsn Ile Lys Ser 20 25 30 Leu 549 58 PRT Homo sapiens 549 Leu Val Cys TyrCys Ser Thr Lys Lys Glu Lys Lys Leu His Glu Ile 1 5 10 15 Ala Ile GlnGln Gly Gln Asn Trp Arg Trp Leu Leu Phe Tyr Lys Glu 20 25 30 Ile Ser ValPro Gly Phe Gln Ser Val Trp Cys Ser Tyr Lys Cys Leu 35 40 45 Cys Val ValTrp Lys Ala Gly Glu Gly Gly 50 55 550 36 PRT Homo sapiens 550 Arg ArgSer Cys Ser Gly Pro Pro Leu Val Asn Thr Ala Gly Lys Ile 1 5 10 15 LeuSer Ser Ser Pro Ala Lys Leu Ala Cys Lys Arg Thr Asp Phe His 20 25 30 IlePro Ser Ile 35 551 37 PRT Homo sapiens 551 Arg Ala Ser Ile Leu Gly IleAsp Asn Glu Arg Gly Cys His Phe Arg 1 5 10 15 His Phe Asn Pro Leu LysGlu Tyr Lys Arg Lys Lys Lys Glu Asn Lys 20 25 30 Ser Phe Arg Ile Val 35552 77 PRT Homo sapiens 552 Ser Lys Asn Lys Thr Arg Gly Gly Asp Trp CysVal Thr Val Leu Arg 1 5 10 15 Lys Arg Arg Lys Ser Phe Met Lys Ser ProPhe Ser Lys Asp Arg Thr 20 25 30 Gly Asp Gly Phe Ser Phe Thr Lys Lys SerLeu Ser Gln Ala Phe Ser 35 40 45 Leu Phe Gly Val His Thr Ser Val Cys ValLeu Cys Gly Arg Arg Gly 50 55 60 Lys Ala Gly Glu Gly Gly Pro Val Gln GlyPro Leu Trp 65 70 75 553 55 PRT Homo sapiens 553 Met Lys Ser Pro Phe SerLys Asp Arg Thr Gly Asp Gly Phe Ser Phe 1 5 10 15 Thr Lys Lys Ser LeuSer Gln Ala Phe Ser Leu Phe Gly Val His Thr 20 25 30 Ser Val Cys Val LeuCys Gly Arg Arg Gly Lys Ala Gly Glu Gly Gly 35 40 45 Pro Val Gln Gly ProLeu Trp 50 55 554 24 PRT Homo sapiens 554 Met Gly Glu Ser Glu Cys TyrArg Arg Leu Ser Gly Ala Ser Cys Thr 1 5 10 15 Trp Thr Val His Val AspPhe Ala 20 555 33 PRT Homo sapiens 555 Met His Cys Gly Thr Arg Val TrpLys Thr Met Lys His Asp Tyr Phe 1 5 10 15 Leu Leu Ala Cys Leu Ser MetThr Ser Thr Gly Gly Ile Leu Cys Thr 20 25 30 Leu 556 67 PRT Homo sapiens556 Ser Thr Leu Ser Leu Ile Pro Thr Ser Ser Ser Leu Ser Phe Trp Pro 1 510 15 Trp Cys Thr Ala Ile Ile Gly Ser Ile Phe Thr Tyr Cys Val Cys Val 2025 30 Cys Val Cys Phe Val Val Met Asn Arg Thr Cys Tyr Leu Pro Asn Ser 3540 45 Ile Ile Tyr His Asn Ser Lys Leu Ala Thr Ile Ile Asp Lys Ser Met 5055 60 Thr Leu Ser 65 557 20 PRT Homo sapiens 557 Met Trp Ile Leu Pro LysVal Ser Leu Ile Cys Ile Val Glu Leu Gly 1 5 10 15 Tyr Gly Lys Pro 20 55862 PRT Homo sapiens 558 Met Ser Thr Gly Asp Gly Arg Asp Ala Glu Lys GlyTrp Pro Val Ser 1 5 10 15 Glu Glu Glu Asn Gln Arg Ser Val Tyr Pro GlyTyr Pro Glu Cys Asp 20 25 30 Glu Arg Gln Ala Val Pro Gln His Cys Ala IleAla Ser Pro Ser Ser 35 40 45 Leu Gln Ser His His Pro Ala Ser Ala Cys ValPro Arg Arg 50 55 60 559 38 PRT Homo sapiens 559 Gln Gln Met Thr Leu GlyThr Lys Ile Lys Trp Gly Gln Leu Gln Arg 1 5 10 15 Gly Gln Glu Ile ProThr Gly Asp Phe Thr Val Arg Asn Phe Met Arg 20 25 30 Phe Ser Ile Ile TyrCys 35 560 31 PRT Homo sapiens SITE (11) Xaa equals any of the naturallyoccurring L-amino acids 560 Pro Phe Leu Phe Cys Ala Ser Arg Ile Arg XaaGln Gly Ile Gly Ile 1 5 10 15 His Gly Gln Val Ala Cys Ser Ala Val ArgMet Tyr Asn Asn Arg 20 25 30 561 45 PRT Homo sapiens 561 Val Leu Cys GluGlu Ala Gly Gln Lys Val Pro Ser Thr Pro Ser Trp 1 5 10 15 Ser Ser TrpThr Leu Gln Lys Arg Leu Arg Gly Ser Pro Ala Glu Ala 20 25 30 Asn Cys SerPro Ser Phe Pro Ala Pro Pro Gly Lys Glu 35 40 45 562 103 PRT Homosapiens 562 Met Ser Leu Ser Ala Leu Ala Cys Asp Phe Thr Pro Ile Gln ProTrp 1 5 10 15 Glu Trp Glu Glu Tyr Glu Gln Ile Thr Leu Gly Leu Thr AlaPro Ser 20 25 30 Asn Leu Leu Glu Ser Asn Tyr Leu Gly Gln Ala Ser Glu CysPhe Val 35 40 45 Arg Lys Leu Val Arg Arg Phe Pro Gln Leu Leu Pro Gly ProPro Gly 50 55 60 His Cys Arg Lys Asp Leu Gly Asp Pro Gln Gln Arg Pro IleAla Leu 65 70 75 80 Leu Pro Ser Leu Pro His Gln Glu Arg Asn Asn Val HisArg Leu Glu 85 90 95 Ala Asp Ser Glu Val Asp Leu 100 563 46 PRT Homosapiens 563 Cys Val Asp Phe Asp Glu Tyr Phe Ser Ser Trp Glu Pro Leu LeuLys 1 5 10 15 Met Met Phe Lys Gly Val Val Gly Gly Lys Met Lys Ala TrpArg Arg 20 25 30 Lys Lys Arg Arg Lys Pro Leu Pro Tyr Lys Ile His Ala Asp35 40 45 564 30 PRT Homo sapiens 564 Met Met Phe Lys Gly Val Val Gly GlyLys Met Lys Ala Trp Arg Arg 1 5 10 15 Lys Lys Arg Arg Lys Pro Leu ProTyr Lys Ile His Ala Asp 20 25 30 565 37 PRT Homo sapiens 565 Leu Ile SerSer Val Asn Lys Thr Lys Gln Lys Arg Ser Asp Ala Thr 1 5 10 15 Leu SerHis Lys His Asp Arg Leu Leu Asn His Phe Val Phe Phe Gly 20 25 30 Asn SerTyr Asn Tyr 35 566 127 PRT Homo sapiens SITE (95) Xaa equals any of thenaturally occurring L-amino acids 566 Ser Ser Lys Phe Pro Ser Asp MetLeu Leu Arg Ile Gln Gln Ile Ile 1 5 10 15 Tyr Cys His Lys Leu Thr IleIle Leu Thr Lys Trp Arg Asn Thr Ala 20 25 30 Arg His Lys Ser Lys Lys LysGlu Asp Glu Leu Ile Leu Lys His Glu 35 40 45 Leu Gln Leu Lys Lys Trp LysAsn Arg Leu Ile Leu Lys Arg Ala Ala 50 55 60 Ala Glu Glu Ser Asn Phe ProGlu Arg Ser Ser Ser Glu Val Phe Leu 65 70 75 80 Val Asp Glu Thr Leu LysCys Asp Ile Ser Leu Leu Pro Glu Xaa Ala 85 90 95 Ile Leu Gln Val Cys MetAsn Ser Val Tyr Ile Ile Tyr Tyr Asn Leu 100 105 110 Pro Ser Val Val ValHis Ala Cys Asn Pro Ser Cys Leu Gly Gly 115 120 125 567 11 PRT Homosapiens 567 Ser Leu Glu Ser Thr Asn Ala Ile Lys Ser Asn 1 5 10 568 19PRT Homo sapiens 568 Ile Arg Pro Asn Lys Asn Asp Gln Met Arg His Cys LeuIle Asn Met 1 5 10 15 Ile Asp Tyr 569 37 PRT Homo sapiens 569 Ile ThrLeu Cys Phe Leu Glu Thr Ala Ile Thr Ile Asn Ile Tyr Ser 1 5 10 15 AsnLeu Val Asn Phe Leu Gln Ile Cys Tyr Cys Gly Tyr Asn Arg Ser 20 25 30 SerIle Val Thr Ser 35 570 31 PRT Homo sapiens 570 Ile Ser Phe Arg Tyr AlaIle Ala Asp Thr Thr Asp His Leu Leu Ser 1 5 10 15 Gln Ala Asn His TyrPro Asn Lys Met Ala Glu Tyr Ser Lys Thr 20 25 30 571 86 PRT Homo sapiensSITE (18) Xaa equals any of the naturally occurring L-amino acids 571Pro Gln Ile Lys Leu Leu Asn Ser Asp Ala Leu Gly Met Arg Thr Thr 1 5 1015 Ser Xaa Asp Leu Val Pro Cys Asn Gln Cys Phe Ile Pro Leu Pro Pro 20 2530 Ser Cys Asn Arg Ile Ala Ser Arg Lys Ala Val Asn Trp Lys Gln Gln 35 4045 Arg Leu Pro Ala Val Arg Gly Leu Leu Asn Asn Ala Pro His Arg Arg 50 5560 Pro Pro Thr Pro Arg Thr Pro Cys Val Phe Pro Ser Glu Gly Pro Lys 65 7075 80 Gly Tyr Gly Phe His Val 85 572 39 PRT Homo sapiens SITE (5) Xaaequals any of the naturally occurring L-amino acids 572 Glu Gln Leu AlaXaa Ile Ser Cys Arg Val Ile Asn Val Ser Phe Arg 1 5 10 15 Cys Leu HisHis Val Ile Glu Ser Leu Pro Glu Arg Gln Leu Thr Gly 20 25 30 Ser Ser ArgGly Ser Gln Pro 35 573 73 PRT Homo sapiens SITE (45) Xaa equals any ofthe naturally occurring L-amino acids 573 Glu Asp Cys Ser Thr Met ProPro Ile Ala Ala Pro Pro Pro Leu Ala 1 5 10 15 Pro Leu Val Phe Ser ProLeu Arg Gly Pro Arg Val Met Ala Phe Met 20 25 30 Ser Arg Cys Gly Asp ArgGly Gly Arg Gly Arg Ser Xaa Ala Gly Arg 35 40 45 Gly Trp Pro Trp Ser GluSer Gly Val Ile Asn Ala His Pro Lys Lys 50 55 60 Arg Pro Cys Pro Gly ProMet Leu Ser 65 70 574 48 PRT Homo sapiens 574 Glu Phe Gly Thr Arg ArgGln Trp Gly Thr Arg Cys Phe Pro Pro Leu 1 5 10 15 Val Gly Arg Lys GlnSer Ala Leu Arg Arg Arg Glu Gly Lys Ala Arg 20 25 30 Ala Gly Arg Cys CysGly Lys Arg Ser Val Lys Ala Gly Phe Asp Ala 35 40 45 575 52 PRT Homosapiens 575 Ala Phe Phe Leu Leu Gln Ala Leu Glu Ile Gln Ser Gln Leu AlaThr 1 5 10 15 Pro Ala Ser Ser Thr Ala Arg Asn Pro Ala Pro Asp Leu HisHis Pro 20 25 30 His Gln Pro Thr Ile Glu Arg Phe Cys Arg His Ser Ser SerTrp Glu 35 40 45 Arg Ile Glu Tyr 50 576 42 PRT Homo sapiens 576 Ala ThrVal Pro Gly Ser Ile Tyr Asn Tyr Phe Tyr His Tyr Asn Ala 1 5 10 15 GlyAla Leu Lys Pro Glu His Ala Ser Glu Ser Pro Arg Gly Leu Cys 20 25 30 AlaGln Thr Ala Gly Pro Phe Pro Ser Phe 35 40 577 56 PRT Homo sapiens 577Ile Arg His Glu Pro Pro Pro Pro Arg Phe Lys Arg Phe Ser Cys Leu 1 5 1015 Ser Leu Leu Ser Ser Trp Asp Tyr Arg Arg Ala Pro Pro His Val Ala 20 2530 Ile Phe Cys Thr Leu Ser Arg Asp Gly Val Leu Pro His Trp Pro Gly 35 4045 Trp Ser Gln Thr Pro Asp Leu Lys 50 55 578 72 PRT Homo sapiens 578 SerThr His Leu Gly Leu Pro Arg Cys Trp Asp Tyr Arg His Glu Pro 1 5 10 15Leu Cys Leu Ala Pro Phe Thr Thr Ile Ser Ile Ile Ile Met Gln Gly 20 25 30Leu Ser Asn Leu Ser Met Pro Gln Asn Pro Pro Glu Gly Cys Ala His 35 40 45Arg Leu Leu Asp Leu Ser Pro Ala Ser Asp Ser Val Pro Pro Glu Trp 50 55 60Gly Ser Lys Ile Ala Phe Glu Val 65 70 579 26 PRT Homo sapiens 579 LeuArg Val Gly Gly Thr Ser Glu Asn Cys Cys Arg Gly Glu Cys Cys 1 5 10 15Gly Ser Val Cys Ile Pro Pro Gly Arg Leu 20 25 580 40 PRT Homo sapiens580 Met Cys Val Thr Arg Met His Val Lys Cys Pro Pro Pro Ser Ala Ser 1 510 15 Val Thr Ala Val Lys Trp Pro Leu Ser Trp Ser Ser Ser Ser Phe Cys 2025 30 Ile Ser Leu His Ala Gly Arg His 35 40 581 36 PRT Homo sapiens 581Glu Glu Arg Asn Lys Asn His Leu Ser Cys Gln Gly Leu Ser Thr Ile 1 5 1015 Cys Cys Ser Tyr Leu Ser Ser Lys Gly Glu His Leu Arg Asn Leu Ser 20 2530 Pro Tyr Ser Phe 35 582 46 PRT Homo sapiens 582 Gly Leu Cys Met ValHis Ser Leu Leu Thr Ser Ser Leu Gly Gly Arg 1 5 10 15 Cys Cys Asn TyrPro Tyr Ile Ala Asp Lys Asp Ile Glu Thr Glu Val 20 25 30 Lys Pro Pro SerGln Gly His Thr Trp His Leu His Cys Ser 35 40 45 583 75 PRT Homo sapiens583 Gln Leu Trp Cys Ile Thr Ala Leu Pro Ser Thr Arg His Cys Ser Lys 1 510 15 Gly Phe Ala Trp Phe Thr His Ser Leu Arg His Pro Ser Val Ala Gly 2025 30 Ala Val Ile Ile Leu Ile Leu Gln Thr Arg Thr Leu Arg Gln Arg Ser 3540 45 Ser His Leu Pro Lys Gly Thr His Gly Ile Cys Thr Ala Pro Asp Arg 5055 60 Pro Thr Glu Arg Ala Ala Val Thr Ile Leu Lys 65 70 75 584 39 PRTHomo sapiens 584 Ser Phe Asp Asn Asn Asn Ser Tyr Gly Val Ser Gln Leu TyrGln Val 1 5 10 15 Pro Asp Thr Val Leu Arg Ala Leu His Gly Ser Leu ThrPro Tyr Val 20 25 30 Ile Pro Arg Trp Gln Val Leu 35 585 38 PRT Homosapiens 585 Asp Arg Gly Gln Ala Thr Phe Pro Arg Ala His Met Ala Ser AlaLeu 1 5 10 15 Leu Leu Thr Asp Arg Gln Arg Glu Leu Leu Ser Arg Ser SerAsn Glu 20 25 30 Leu Cys Met Ser Lys Val 35 586 73 PRT Homo sapiens SITE(66) Xaa equals any of the naturally occurring L-amino acids 586 Leu LeuLeu Ile Leu Arg Pro Phe Leu Asn Ser Gln Phe Lys Leu Gln 1 5 10 15 LeuPro Leu Val Leu Phe His Ser Ser Cys Thr Tyr Ile Cys Leu Leu 20 25 30 TyrAsn Tyr Glu Leu Phe His Ile Val Ala Leu Thr Gly Lys Leu Met 35 40 45 AsnLeu Gly Leu His Leu Phe Ala His His Leu Ile Leu Ala Val Ala 50 55 60 HisXaa Gly Cys Ser Ile Pro Ile Tyr 65 70 587 37 PRT Homo sapiens 587 ThrHis Asn Ser Asn Tyr Ser Ser Leu Trp Phe Ser Ser Thr Ala Val 1 5 10 15Val Leu Thr Tyr Val Tyr Tyr Ile Ile Met Asn Cys Phe Ile Leu Ser 20 25 30Pro Leu Gln Val Asn 35 588 53 PRT Homo sapiens 588 Thr Leu Val Ala GlySer Pro Cys Ser Leu Ser Arg Trp Ile Met Ala 1 5 10 15 Gly Phe Cys HisGly Glu Leu Val Gln Ser Asp Met Glu Ser Gln Glu 20 25 30 Trp Glu Arg GlyGln Val Val Leu Ser His Thr Ser Leu Pro Trp Cys 35 40 45 Tyr Val Ser ProArg 50 589 39 PRT Homo sapiens 589 Met Ala Gly Phe Cys His Gly Glu LeuVal Gln Ser Asp Met Glu Ser 1 5 10 15 Gln Glu Trp Glu Arg Gly Gln ValVal Leu Ser His Thr Ser Leu Pro 20 25 30 Trp Cys Tyr Val Ser Pro Arg 35590 94 PRT Homo sapiens 590 Met Ala Val Trp Ile Ser Gly Ser Tyr Ser SerPhe Cys Ser Arg Ser 1 5 10 15 Asn Trp Asp Val Phe Ser Pro Asn Ile ValLeu Ala Ser Leu Pro Phe 20 25 30 Ser Phe Arg Ser Val Ser Lys Ala Ala LysPro Trp Trp Leu Ala Leu 35 40 45 Pro Ala Leu Phe Pro Asp Gly Leu Trp LeuAsp Ser Ala Met Gly Ser 50 55 60 Leu Tyr Ser Gln Thr Trp Lys Ala Arg AsnGly Lys Glu Val Arg Trp 65 70 75 80 Phe Ser Pro Thr Pro His Cys Leu GlyAla Met Ser His Leu 85 90 591 19 PRT Homo sapiens 591 Gly Trp Leu TyrGly Ser Val Gly Leu Ile Pro His Ser Ala Ala Glu 1 5 10 15 Ala Thr Gly592 82 PRT Homo sapiens 592 Arg Ser Lys Arg Gln Ser Gln Gly Ser Arg CysSer Val Pro Leu Leu 1 5 10 15 Ala Gln Gln Ser Arg Ser Pro Pro Val ProLeu Gln Ala Gln Pro Ala 20 25 30 Trp Leu Leu Gly Ser Glu Thr Ile Ala TrpSer Gly Gly Gly Ser Gly 35 40 45 Trp Glu Gly Pro Arg Asp Pro Gly Thr SerThr Ala Ala Gly Asn Ser 50 55 60 Gly Pro Gly Ile Gly Met Gly His Arg ThrPro Pro Pro Ser His Thr 65 70 75 80 Gly Arg 593 30 PRT Homo sapiens 593Arg Trp Asp Pro Ala Trp Gly Leu Asp Ile Pro Glu Ser Ser Cys Pro 1 5 1015 Val Thr Met Gly Glu Leu Arg Ser Gly Asp Gly Ile Val Leu 20 25 30 59450 PRT Homo sapiens 594 Gly Ala Leu Leu Trp Asp Asn Ser Met Ile Ser AlaPro Arg Gly Ser 1 5 10 15 His Arg Glu Ala Gly Ala Leu Phe Pro Ser TrpLeu Ser Asn Pro Ala 20 25 30 Val Leu Pro Ser Arg Ser Arg Pro Ser Gln ProGly Cys Leu Asp Pro 35 40 45 Arg Gln 50 595 49 PRT Homo sapiens 595 AsnSer Ala Arg Glu Pro Arg Arg Trp Ile Arg Pro Thr Arg Gly Ser 1 5 10 15Gly Glu Thr Thr Ala Pro Cys Cys Phe Glu Pro Leu Asn Gly Gly Thr 20 25 30Leu Val His Ala Ala Ala Met Ala Arg Ala Ser Glu Ala Ala Gly Thr 35 40 45Gly 596 11 PRT Homo sapiens 596 Met Ala Arg Ala Ser Glu Ala Ala Gly ThrGly 1 5 10 597 84 PRT Homo sapiens 597 Cys Phe Thr Thr Ala Phe Gln LysAla Leu Arg Asp Pro Arg Pro Thr 1 5 10 15 Leu Pro Asp Thr His Gly SerLeu Arg Asn Ala Pro Leu Lys Ser Leu 20 25 30 Thr Leu Pro Ala Ala Phe ValVal Ser Phe Phe Phe Leu Ser Leu Leu 35 40 45 Gln Asp Gly Ile Lys Glu ArgSer Gln Thr Gln Asn Ala Thr Phe Phe 50 55 60 Phe His Asp Arg Ser Asp IleGlu Gly Leu Ser Glu Glu Pro Cys Ser 65 70 75 80 Gly Thr Thr Pro 598 95PRT Homo sapiens 598 Leu Ala Leu Gln Glu Ala Val Thr Gly Lys Gln Val LeuCys Ser Pro 1 5 10 15 Pro Gly Ser Ala Ile Pro Gln Ser Ser Arg Pro AlaPro Gly Pro Ala 20 25 30 Ser Leu Ala Ala Trp Ile Arg Asp Asn Ser Leu ValTrp Arg Arg Leu 35 40 45 Arg Val Gly Gly Thr Gln Gly Pro Gly His Gln TyrSer Ser Trp Glu 50 55 60 Phe Arg Pro Arg Asp Arg Asp Gly Ala Gln Asp ThrThr Pro Ile Ser 65 70 75 80 His Arg Glu Met Lys Val Gly Ser Ser Met GlyThr Gly His Pro 85 90 95 599 47 PRT Homo sapiens 599 Met Ala Gly Arg LeuPhe Thr Leu Leu Leu Trp Gln Glu Leu Ala Arg 1 5 10 15 Arg Leu Val ProGly Asp Ala Ser Pro Arg Leu Ser Arg Lys Arg Ser 20 25 30 Val Thr Pro GlyPro Pro Phe Pro Thr Leu Thr Val Pro Ser Glu 35 40 45 600 42 PRT Homosapiens 600 Met Phe Tyr Ser Lys Ile Phe Tyr Phe Leu Leu Leu Asn Ser AspThr 1 5 10 15 Ser Asn Asn Val Thr Ser Lys Thr Leu Val Ser Ser Ile SerSer Ser 20 25 30 Asn Asn Arg Leu Ala Val Ser Ile Val Phe 35 40 601 47PRT Homo sapiens 601 Ser Arg Gln Lys Asn Leu Leu Lys Leu His Ser Asn ProAsn Cys Asp 1 5 10 15 Asn Phe Cys Phe Ile Phe Asn Tyr Lys Pro Lys TyrIle Cys Ile Phe 20 25 30 Lys Leu Ile Cys Leu Lys Ile Leu Leu Tyr Ile PheGly Ser Gly 35 40 45 602 56 PRT Homo sapiens SITE (24) Xaa equals any ofthe naturally occurring L-amino acids 602 Met Leu Leu Ser Leu Leu MetVal Phe Thr Ser Glu Leu Tyr Val Lys 1 5 10 15 Arg His Ile Ser Phe LysSer Xaa Asp Lys Pro His Cys His Lys Asn 20 25 30 Gln Asp Ile Asp Val LeuPhe Arg Lys Leu Leu Glu Lys His Phe Lys 35 40 45 Val Ile Asn Met Ile CysPhe Pro 50 55 603 12 PRT Homo sapiens 603 Phe Arg Glu Tyr Gly Phe TyrAsn Leu His Phe Cys 1 5 10 604 38 PRT Homo sapiens 604 Leu Val Thr ThrAsp Tyr Tyr Asp Gly Cys Asn Glu Asp Tyr Glu Tyr 1 5 10 15 Asn Trp SerTyr Met Phe Leu Asn Ser Glu Gln Leu Phe Ile Lys Phe 20 25 30 Tyr Pro ThrPhe Phe Cys 35 605 52 PRT Homo sapiens 605 Asn Val Ile Ala Pro Gly LeuGlu Ser Ser Cys Ala Asn Ser Leu Phe 1 5 10 15 Leu Leu Phe Val Cys LeuPro Val Ala His His Arg His Asn Phe Leu 20 25 30 Phe Ile Lys His Ser LeuTyr Asn His Leu Arg Asp Tyr Glu Ser Asp 35 40 45 Phe Asp Lys Ile 50 60634 PRT Homo sapiens 606 Pro Lys Val Leu Ala Val Leu Lys Lys Lys Asn HisVal Ala Leu Ser 1 5 10 15 Ile Phe Glu Leu Leu Ser Asn Asp Ile Cys SerPhe Ile Ser Phe Phe 20 25 30 Met Ser 607 28 PRT Homo sapiens 607 Glu GlyPro Asp Ile Asn Ser Asn Leu Lys Phe Leu Leu Cys Leu Lys 1 5 10 15 LysLys Ile Met Trp Pro Phe Gln Tyr Leu Asn Cys 20 25 608 47 PRT Homosapiens 608 Leu Leu Ser Leu Ile Leu Leu Arg Ile Trp Tyr Asp Phe Ser LysGln 1 5 10 15 Thr Val Phe Trp Phe Phe Leu Asn Val Phe Asn Phe Phe SerSer Cys 20 25 30 Asn Asn Asp Gly Ala Cys Ser Tyr Lys Tyr Arg Lys Val GlnIle 35 40 45 609 12 PRT Homo sapiens 609 His Thr Leu Phe Ile Ser Phe LeuTrp Ala Glu Gly 1 5 10 610 28 PRT Homo sapiens 610 Met Leu Pro Val PheVal Leu Phe Phe Cys Phe Thr Tyr Ser Ala Arg 1 5 10 15 Lys Gln Ser ValPhe Lys Lys Gly Asn Val Phe Glu 20 25 611 63 PRT Homo sapiens 611 SerPro Cys Ser Ala Ala Glu Cys His Asn Leu Ser Leu Leu Ser Ser 1 5 10 15Cys Ser Leu Val Ser Ser Asn Ile Leu Phe Ser Phe Pro Phe Phe Gly 20 25 30Gln Lys Ala Arg Cys Cys Leu Phe Leu Phe Tyr Phe Ser Ala Ser His 35 40 45Ile Ala His Glu Ser Arg Val Tyr Ser Lys Lys Glu Met Cys Leu 50 55 60 61265 PRT Homo sapiens 612 His Lys Cys Phe Gln Cys Phe Ile Leu Ala Asn GlyPhe Leu Lys Val 1 5 10 15 Ile Lys Pro Phe Gln Arg Asn Trp Ser Asp LysThr Phe Phe Leu Val 20 25 30 Cys Leu Asn Lys Ala Ile Ser Glu Ala Leu LeuSer Lys Met Thr Phe 35 40 45 Leu Ser Phe Phe Lys Thr Asn Leu Leu Leu LeuGlu Thr Phe Cys Thr 50 55 60 Ile 65 613 99 PRT Homo sapiens 613 Leu LeuGly Val Leu Lys Pro Leu Tyr Phe Ser Val Glu Pro Val Leu 1 5 10 15 GlyGlu Arg Ser Val Ala Phe Glu Glu Val Arg Glu Lys Asn His Gly 20 25 30 ThrSer Gly Phe Leu Ser Leu Tyr Ser Leu Ala Ala Ile Val Cys Gly 35 40 45 HisLeu Met Phe Phe His Thr Leu Leu Gly Arg Gly Gly Asn Asp His 50 55 60 ProGly Gln Ser Pro Leu Pro Gly Met Arg Pro Leu Arg Gly Gly Leu 65 70 75 80Ala Gly Gln Ala Pro Ser Gly His Pro Trp Met Gln Pro Leu Asp Thr 85 90 95Cys Leu Leu 614 43 PRT Homo sapiens 614 Arg Pro Thr Arg Pro Pro Thr ArgPro Asp Arg Pro Ser Leu Glu Leu 1 5 10 15 Ala Pro Gly Leu Cys Ala AspPhe Leu Gly Ser Ser Asn His Cys Ile 20 25 30 Phe Leu Leu Ser Leu Tyr LeuGly Arg Asp Gln 35 40 615 49 PRT Homo sapiens 615 Glu Lys Arg Ile MetVal Pro Gln Gly Phe Phe Pro Phe Thr Arg Trp 1 5 10 15 Gln Pro Leu SerVal Gly Thr Ser Cys Phe Ser Thr Leu Tyr Trp Ala 20 25 30 Val Glu Val ThrIle Thr Gln Ala Ser Leu Leu Cys Leu Gly Cys Ala 35 40 45 Leu 616 123 PRTHomo sapiens 616 Met Thr Leu Asp Glu Trp Lys Asn Leu Gln Glu Gln Thr ArgPro Lys 1 5 10 15 Pro Glu Phe Asn Ile Arg Lys Pro Glu Ser Thr Val ProSer Lys Ala 20 25 30 Val Val Ile Arg Glu Ser Lys Tyr Arg Asp Asp Met ValLys Asp Asp 35 40 45 Tyr Glu Asp Asp Ser His Val Phe Arg Lys Pro Ala AsnAsp Ile Thr 50 55 60 Ser Gln Leu Glu Ile Asn Phe Gly Asn Leu Pro Arg ProGly Arg Gly 65 70 75 80 Ala Arg Gly Gly Thr Arg Gly Gly Arg Gly Arg IleArg Arg Ala Glu 85 90 95 Asn Tyr Gly Pro Arg Ala Glu Val Val Met Gln AspVal Ala Pro Asn 100 105 110 Pro Asp Asp Pro Glu Asp Phe Pro Ala Leu Ser115 120 617 100 PRT Homo sapiens 617 Cys Lys Met Leu Pro Pro Thr Gln MetThr Arg Lys Ile Ser Leu Arg 1 5 10 15 Cys Leu Glu Arg Ala Leu Phe ProSer Thr Ala Glu Leu His Cys Thr 20 25 30 Pro Val Gly Arg Leu Phe Gln LeuGly Gln Gly Ser Gln Thr Leu Arg 35 40 45 Thr Ile Asp Val Ala Phe Pro ValSer Cys Lys Phe Val Ala Leu Phe 50 55 60 Trp Ala Glu Leu Leu Glu Gly LeuLeu Gln Arg Leu Glu Ser Arg Pro 65 70 75 80 Phe Pro Lys Lys Met Lys AsnGly Asp Cys Val Phe Ile Glu Gly Ile 85 90 95 Ser Asn Glu Glu 100 618 41PRT Homo sapiens 618 Pro Pro Ser Ser Trp Ala Trp Ser Gln Arg Arg His ProGly Arg Pro 1 5 10 15 Gly Lys Asp Gln Glu Gly Arg Glu Leu Trp Thr GlnSer Arg Ser Gly 20 25 30 Asp Ala Arg Cys Cys Pro Gln Pro Arg 35 40 61922 PRT Homo sapiens 619 Cys Leu Lys Cys Val Tyr Arg Asp Ser Ile Asp SerSer Ala Glu Ala 1 5 10 15 Trp Arg Glu Arg Arg Leu 20 620 29 PRT Homosapiens 620 Leu Ser Tyr Ser Val Leu Leu Ile Leu Pro Leu Phe His Ser LeuPro 1 5 10 15 Thr Leu Lys Asp Thr His Thr His Asn Lys Trp Val Glu 20 25621 61 PRT Homo sapiens 621 Glu Val Asn Gly Val Gly Tyr Lys His Ser CysPhe Ser Asp Ile Ser 1 5 10 15 Ser Val Leu Glu Asn Lys Asp Ser Arg MetArg Ala Pro His Tyr Ala 20 25 30 Ser Phe Gln His Phe Phe Ser Val Leu LeuLys Leu Ser Pro Gln Ala 35 40 45 Cys Leu Thr Glu Ser Gln Cys Ile Pro LeuThr Phe Tyr 50 55 60 622 37 PRT Homo sapiens 622 Lys Thr His Thr His ThrIle Ser Gly Trp Ser Lys Lys Ser Thr Glu 1 5 10 15 Leu Asp Ile Ser IlePro Ala Phe Leu Thr Ser Pro Val Ser Trp Arg 20 25 30 Thr Arg Ile Leu Glu35 623 29 PRT Homo sapiens 623 Ile Arg His Glu Leu Gly Ser Ser Asp ProPro Ala Glu Ala Ser Gln 1 5 10 15 Ile Ala Gly Thr Ala Ala Val Ser HisHis Ala Gln Pro 20 25 624 25 PRT Homo sapiens 624 Met Leu Tyr Leu IleLeu Ile Ser Leu Ser Ser Leu Ser Phe Ser Phe 1 5 10 15 Ser Leu Pro ProPhe Ser Ile Ile Ile 20 25 625 24 PRT Homo sapiens 625 Ser Ser Tyr PheLeu Arg His Phe Arg Ile Tyr His Thr Cys Pro Lys 1 5 10 15 Tyr Phe SerMet Asn Ile Ile Asn 20 626 69 PRT Homo sapiens 626 Lys Leu Thr Leu ThrLys Gly Asn Lys Ser Trp Ser Ser Thr Ala Val 1 5 10 15 Ala Ala Ala LeuGlu Leu Val Asp Pro Pro Gly Cys Arg Asn Ser Ala 20 25 30 Arg Asp Ser LeuPro Asn Ser Thr Met Met Phe Tyr Tyr Ala Cys Phe 35 40 45 Ile Leu Tyr SerSer Leu Ser Pro Leu Ser Leu Ser Leu Ser Pro Ser 50 55 60 Leu Leu Ser LeuLeu 65 627 14 PRT Homo sapiens 627 Gln Phe His Thr Gly Asn Ser Tyr AspHis Asp Tyr Ala Lys 1 5 10 628 35 PRT Homo sapiens 628 Ala Val Cys ThrGly Gly Tyr Cys Glu Ser Cys Arg Cys Glu His Cys 1 5 10 15 Val Cys ValCys Val Asp Leu Cys Val Leu Phe Ser Gly Lys Glu Leu 20 25 30 Arg Val Arg35 629 72 PRT Homo sapiens 629 Val Ser Phe Phe Phe Val Phe Lys Trp SerPhe Ala Glu Ile Lys Ser 1 5 10 15 Arg Glu Glu His Trp Ala Ser Leu ThrPro Lys Pro Thr Leu Leu Ser 20 25 30 Ala Leu Leu Thr Cys Asp Val Leu LysSer Ser Ile Ile Phe Lys Cys 35 40 45 Cys Glu Ser Thr Glu Asp Lys Gly PheAsp Ser Phe Phe Gln Ala Ser 50 55 60 Lys Asp Gly Ser Ser Ser Arg Ile 6570 630 99 PRT Homo sapiens 630 Arg Ser Trp Gly Ser Gln Arg Ser Leu CysLeu Leu Phe Ile Pro Phe 1 5 10 15 Ala Ala Glu Ser Tyr Ser Val Val TrpMet Gly His Leu Phe Val Val 20 25 30 Cys Leu Leu Ser Ser Trp Trp Thr PheArg Pro Phe Ala Leu Ala Val 35 40 45 Thr Val Asn His Val Ala Val Asn IleVal Cys Val Ser Ala Trp Thr 50 55 60 Cys Val Ser Cys Ser Leu Gly Arg SerCys Gly Leu Glu Gly Ser Phe 65 70 75 80 Leu Phe Pro Leu Glu Thr Leu TrpPhe Pro His Met Val Val Leu Cys 85 90 95 Leu Thr Phe 631 74 PRT Homosapiens 631 Met Gly His Leu Phe Val Val Cys Leu Leu Ser Ser Trp Trp ThrPhe 1 5 10 15 Arg Pro Phe Ala Leu Ala Val Thr Val Asn His Val Ala ValAsn Ile 20 25 30 Val Cys Val Ser Ala Trp Thr Cys Val Ser Cys Ser Leu GlyArg Ser 35 40 45 Cys Gly Leu Glu Gly Ser Phe Leu Phe Pro Leu Glu Thr LeuTrp Phe 50 55 60 Pro His Met Val Val Leu Cys Leu Thr Phe 65 70 632 51PRT Homo sapiens 632 His Asp Val Leu Gly Ala Arg Asn Ala Ala Cys Val CysCys Ser Phe 1 5 10 15 Leu Leu Gln Gln Asn Arg Ile Leu Leu Phe Gly TrpAla Thr Cys Leu 20 25 30 Leu Ser Val Tyr Ser Pro Ala Gly Gly His Leu GlyArg Leu His Trp 35 40 45 Arg Leu Leu 50 633 130 PRT Homo sapiens 633 MetLeu Asp Phe Lys Thr Ser Gln Val Ser Lys Ala Leu Lys Arg Val 1 5 10 15Gly Phe Gly Val Arg Leu Ala Gln Cys Ser Ser Leu Asp Leu Ile Ser 20 25 30Ala Lys Leu His Leu Lys Thr Lys Lys Lys Glu Thr Tyr Ile Thr Ser 35 40 45Thr Val Met Thr Ala Ala Ser Leu Phe Leu Ser Tyr Val Thr Ser Glu 50 55 60Phe Thr Arg Ser Ile Met Ala Thr Phe Tyr Cys Phe Val Leu Lys Leu 65 70 7580 His Ile Gly Glu Met Gly Thr Leu Gln Thr Ala Gly Gly Ser Lys Met 85 9095 Thr Trp Pro Leu Gln Lys Ala Ile Trp Gln Phe Leu Lys Arg Leu Ser 100105 110 Ile Lys Leu Pro Tyr Val Glu Thr Arg Glu Ser Pro Gly Glu Thr Lys115 120 125 Asn Tyr 130 634 28 PRT Homo sapiens 634 Leu Thr Arg Asn SerPhe Pro Glu Asn Arg Thr His Lys Ser Thr Gln 1 5 10 15 Thr His Thr GlnCys Ser Gln Arg His Asp Ser Gln 20 25 635 90 PRT Homo sapiens 635 IleArg His Glu Gly Gln Ser Ser Ser Arg Gly Ser Ser His Cys Asp 1 5 10 15Ser Pro Ser Pro Gln Glu Asp Gly Gln Ile Met Phe Asp Val Glu Met 20 25 30His Thr Ser Arg Asp His Ser Ser Gln Ser Glu Glu Glu Val Val Glu 35 40 45Gly Glu Lys Glu Val Glu Ala Leu Lys Lys Ser Ala Asp Trp Val Ser 50 55 60Asp Trp Ser Ser Arg Pro Glu Asn Ile Pro Pro Lys Glu Phe His Phe 65 70 7580 Arg His Pro Lys Arg Ser Val Ser Leu Ser 85 90 636 40 PRT Homo sapiens636 Gly Ile Leu Leu Thr Leu Tyr Pro Phe Trp Pro Glu Asp Ile Leu Glu 1 510 15 Phe Pro Asn Arg Val Tyr Cys Cys Leu Glu Ile Cys Lys Gly Phe Phe 2025 30 Ser Ala Asn Ala Thr Ser Arg Leu 35 40 637 47 PRT Homo sapiens 637Glu Phe Gly Thr Arg Asp Arg Val Val Pro Glu Ala Val Leu Thr Val 1 5 1015 Thr Ala Leu Arg His Lys Lys Met Gly Arg Ser Cys Leu Met Trp Lys 20 2530 Cys Thr Pro Ala Gly Thr Ile Ala Leu Ser Gln Lys Lys Lys Leu 35 40 45638 52 PRT Homo sapiens 638 Ala His Pro Leu Pro Ala Pro Thr Glu Gly LysGlu Lys Pro Leu Glu 1 5 10 15 Met Arg Val Thr Cys Glu Val Val Tyr CysHis Ser Ser Leu Phe Glu 20 25 30 Leu Glu Thr Ile Val Ser Met Thr Gln ProThr Thr Leu Phe Leu His 35 40 45 Ile Gln Phe Gln 50 639 68 PRT Homosapiens 639 Thr Phe Cys Val Phe Lys His Glu Glu Lys Trp Ser His Glu GluArg 1 5 10 15 Gly Tyr Phe Leu Arg Arg Ile Ser Glu Gly Val His Ser IleSer Leu 20 25 30 Pro Phe Ser Cys Phe Gly Phe Gly Ala Arg His Leu Tyr TrpLys Ala 35 40 45 Thr Glu His Thr Leu Cys Gln His Leu Leu Arg Glu Arg LysSer Pro 50 55 60 Trp Lys Cys Val 65 640 64 PRT Homo sapiens 640 Gln SerLeu Leu Leu Phe Arg Asn Leu Gln Gly Leu Leu Phe Arg Lys 1 5 10 15 CysHis Gln Gln Ile Ile Ile Leu Ser Ala Met Leu Leu Ser Leu Ile 20 25 30 SerAla Thr Arg Leu Asp Leu Tyr His Ser Trp Tyr Lys Phe Tyr Ser 35 40 45 CysAsn Ile Thr Thr Ile Ser Leu Leu Lys Arg Asp Gln Val Ser Lys 50 55 60 64122 PRT Homo sapiens 641 Ile Arg His Glu Glu Ser Phe Asn Pro Leu Thr CysGly Phe Ser Leu 1 5 10 15 Phe Phe Ser Leu Phe Ser 20 642 27 PRT Homosapiens 642 Met Glu Thr Leu Leu Leu Leu Leu Phe Phe Leu Ser Leu Leu IlePhe 1 5 10 15 Arg Phe Arg Ile Leu Val Ser Gln Cys Ile Asn 20 25 643 65PRT Homo sapiens 643 Phe Leu Leu Thr Thr Val Leu Leu Phe Ser Ser Lys ValArg Asp Pro 1 5 10 15 Arg Ala Asn Phe Asp Gln Ser Leu Arg Val Leu LysHis Ala Lys Lys 20 25 30 Val Gln Pro Asp Val Ile Ser Lys Thr Ser Ile MetLeu Gly Leu Gly 35 40 45 Glu Asn Asp Glu Gln Val Tyr Ala Thr Met Lys GlyLys Glu Ile Glu 50 55 60 Lys 65 644 23 PRT Homo sapiens 644 Gln Gln SerCys Cys Phe Pro Val Arg Phe Val Ile Leu Gly Pro Ile 1 5 10 15 Leu IleSer Pro Tyr Val Tyr 20 645 59 PRT Homo sapiens 645 Val Trp Leu Leu SerSer Ile Leu Leu Arg Val Leu Trp Asn Arg Tyr 1 5 10 15 Thr Leu Gln GluLeu Ser Phe Trp Leu Pro Trp Phe Ala Ser Arg Ala 20 25 30 Thr Ser Leu ValLeu Gln His Gly Asp Asn Tyr Leu Leu Phe Leu Phe 35 40 45 Cys Phe Val CysPhe Val Leu Ala Met Pro Phe 50 55 646 26 PRT Homo sapiens 646 Ile ArgHis Glu Val Ser Met Ala Phe Val Phe His Leu Ala Gln Gly 1 5 10 15 ThrLeu Glu Pro Leu Tyr Ile Ala Gly Ala 20 25 647 40 PRT Homo sapiens 647Asn Ser Ala Arg Gly Glu Tyr Gly Phe Cys Leu Pro Ser Cys Ser Gly 1 5 1015 Tyr Phe Gly Thr Ala Ile His Cys Arg Ser Leu Ala Ser Gly Tyr His 20 2530 Gly Leu Leu Pro Glu Gln Gln Ala 35 40 648 26 PRT Homo sapiens 648 HisGlu Leu Thr Val Pro Ser Arg Met Gly Ser Lys Gly Lys Pro Tyr 1 5 10 15Pro Cys Gly Phe Tyr Ser Ser Leu Ile Pro 20 25 649 103 PRT Homo sapiens649 Lys Cys Ile Tyr Pro Lys Pro Ala Arg Thr His His Cys Ser Ile Cys 1 510 15 Asn Arg Cys Val Leu Lys Met Asp His His Cys Pro Trp Leu Asn Asn 2025 30 Cys Val Gly His Tyr Asn His Arg Tyr Phe Phe Ser Phe Cys Phe Phe 3540 45 Met Thr Leu Gly Cys Val Tyr Cys Ser Tyr Gly Ser Trp Asp Leu Phe 5055 60 Arg Glu Ala Tyr Ala Ala Ile Glu Lys Met Lys Gln Leu Asp Lys Asn 6570 75 80 Lys Leu Gln Ala Val Ala Asn Gln Thr Tyr His Gln Thr Pro Pro Pro85 90 95 Thr Phe Ser Phe Arg Glu Arg 100 650 38 PRT Homo sapiens 650 AlaArg Gly His Trp Asn Leu Ile Leu Ile Val Phe His Tyr Tyr Gln 1 5 10 15Ala Ile Thr Thr Pro Pro Gly Tyr Pro Pro Gln Gly Arg Asn Asp Ile 20 25 30Ala Thr Val Ser Ile Cys 35 651 33 PRT Homo sapiens 651 Trp Gln Cys GluLeu Asp Cys Val Ser His Asp Ser Ser Thr His Ser 1 5 10 15 Ala Pro TyrVal Ile Ser Arg Ala Ser Lys Gly Ser Phe Ser Gln Asn 20 25 30 Pro 652 83PRT Homo sapiens 652 Ser Lys Arg Ala Ser Gly Pro Ala Leu Gly Tyr His AlaGly Gln Phe 1 5 10 15 Lys Asp Gln Pro Phe Tyr His Cys Arg Arg Lys ThrGln Cys Gly Glu 20 25 30 Ile Leu Gly Leu Thr Ser Leu Tyr Ser Gly Lys GlnLys Phe Gln Pro 35 40 45 Gln Thr Arg Gly Gln Ala Ala Ser Tyr Leu Pro CysPro Val Leu Thr 50 55 60 Arg Thr Ser Ser Arg Ile Gln His Trp Ser Trp ProPro Pro Leu Leu 65 70 75 80 Leu Ala Val 653 31 PRT Homo sapiens 653 GluSer Leu Gln Leu Arg Leu Leu Gly Gln Leu Glu Gly Ile Pro Gly 1 5 10 15Cys Gly Tyr Arg Lys Ala Leu Ala Tyr Ser Gly Ala Leu Thr Phe 20 25 30 65466 PRT Homo sapiens 654 Ser Leu Ala Pro Trp Glu Trp Asn Glu Leu Gly AlaPro Ser Leu Gly 1 5 10 15 Asp Cys Ser Leu Ser Leu Cys Asp Gly Ser ValSer Trp Thr Val Ser 20 25 30 Ala Thr Thr Arg Ala Leu Ile Leu Leu Pro MetLeu Phe Gln Gly Pro 35 40 45 Pro Arg Ala Ala Phe Leu Arg Ile Leu Asp GlnLys Glu Pro Val Gly 50 55 60 Leu Pro 65 655 72 PRT Homo sapiens 655 ThrAla Thr Leu Asn Ser Phe Phe Gly Gly Trp Gly Leu Ala Leu Leu 1 5 10 15Leu Arg Leu Glu Cys Ser Asp Thr Ile Met Asp His Cys Ser Leu Asp 20 25 30Leu Leu Gly Ser Ser Asn Pro Pro Ala Ser Ala Ser Gln Val Val Gly 35 40 45Thr Thr Gly Ala Arg His His Ala Gln Leu Ile Phe Cys Phe Phe Val 50 55 60Gln Thr Arg Ser His Ser Val Ala 65 70 656 47 PRT Homo sapiens 656 MetAsp His Cys Ser Leu Asp Leu Leu Gly Ser Ser Asn Pro Pro Ala 1 5 10 15Ser Ala Ser Gln Val Val Gly Thr Thr Gly Ala Arg His His Ala Gln 20 25 30Leu Ile Phe Cys Phe Phe Val Gln Thr Arg Ser His Ser Val Ala 35 40 45 65714 PRT Homo sapiens 657 Gly Val Leu Lys Gln Ser Ser His Leu Val Leu SerLys Gly 1 5 10 658 21 PRT Homo sapiens 658 Asp Tyr Ser Cys Glu Ser LeuCys Pro Ala Leu Leu Ser Ile Ala Pro 1 5 10 15 Asp Ile Val Leu Asn 20 65927 PRT Homo sapiens 659 Thr Thr Ile His Lys Thr Gln Leu Gly Ser Tyr LysIle Leu Trp Glu 1 5 10 15 Pro Lys Glu Gly Tyr His Asn Ser Thr Trp Ile 2025 660 9 PRT Homo sapiens 660 Ile Arg Glu Ile Phe Leu Arg Arg Pro 1 5661 24 PRT Homo sapiens 661 Leu Lys Phe Gln Lys Pro Gly Lys Ile Gln MetArg Gly Gly Gly Arg 1 5 10 15 Val Phe Trp Tyr Lys Asn Cys Lys 20 662 30PRT Homo sapiens 662 Asn Ser Ala Arg Val Thr Gln Lys Gly Glu Ser Val GlySer Val Gly 1 5 10 15 Cys Met Arg Ala Ile Ala Gly Phe Asp Asn Tyr ProLeu Phe 20 25 30 663 33 PRT Homo sapiens 663 Gly Thr Ile Gly Ile Phe TrpPro Leu Pro Val Ala Ile Leu Ser Ser 1 5 10 15 Gly Asp Tyr Leu Gln ThrGln Ile His Arg Pro Leu Leu His Arg Gly 20 25 30 Thr 664 20 PRT Homosapiens 664 Leu Pro Leu Pro Leu Ser Ser Leu Leu His Ile Ala Thr Cys AsnPro 1 5 10 15 Phe Pro Lys Thr 20 665 46 PRT Homo sapiens 665 Ser Tyr PhePhe Val Tyr Asn Leu Ile Leu Lys Ile Ile Gln Gly Asp 1 5 10 15 His AlaSer Ile Ile Leu Leu Ala Thr Ile Pro Ile Phe Gly Asp Ile 20 25 30 Tyr TyrVal Lys Gly Gln Leu Ala Ser Phe Gly Pro Tyr Leu 35 40 45 666 21 PRT Homosapiens 666 Leu Phe Tyr His Leu Glu Ile Ile Ser Arg His Lys Ser Ile AlaHis 1 5 10 15 Cys Ser Ile Glu Ala 20 667 12 PRT Homo sapiens 667 Cys SerCys His Cys Pro Ser Arg Ala Phe Ser Thr 1 5 10 668 29 PRT Homo sapiens668 Pro His Ala Ile His Ser Gln Lys Pro Ser Ser Ile Phe Leu Ile Thr 1 510 15 Asp Val Phe Pro Asp Pro Pro Val Gly Ile Tyr Leu Leu 20 25 669 48PRT Homo sapiens 669 Arg Lys Leu Phe His Lys Ile Asn Ser Lys Ser Phe HisLeu Ser Gly 1 5 10 15 Met His Ile Leu Ile Ser Val Trp Ile Val Arg SerArg Ile Ile Lys 20 25 30 Val Lys Tyr Glu Leu Leu Leu Cys Phe Phe Asp ValIle Phe Tyr Val 35 40 45 670 41 PRT Homo sapiens 670 Asn Ser Ala Arg AspVal Phe Phe Thr Gln Lys Ile Leu Tyr Ser Gln 1 5 10 15 Thr Cys Ile PhePhe Pro Cys Leu Val Pro Phe Ser Phe Leu Phe Ser 20 25 30 Phe Phe Phe PheLeu Ser Phe Val Gly 35 40 671 56 PRT Homo sapiens 671 Met Phe Ser SerLeu Lys Lys Phe Tyr Ile Leu Lys His Val Tyr Ser 1 5 10 15 Phe Pro ValLeu Phe His Phe Leu Phe Phe Phe Leu Phe Ser Phe Ser 20 25 30 Phe Leu SerTrp Ala Glu Lys Gly Ala Gly Lys Met Lys Leu Ala Thr 35 40 45 672 39 PRTHomo sapiens 672 Ile Gln Leu Leu Tyr Leu Lys Gly Ala Ala Met Lys Tyr LeuSer Tyr 1 5 10 15 Val Ala Arg Leu Leu Phe Leu Lys Ala Leu Asp Leu PheAla Pro Lys 20 25 30 Met Val Gln Ile Asp Ser Phe 35

What is claimed is:
 1. An isolated nucleic acid molecule comprising apolynucleotide having a nucleotide sequence at least 95% identical to asequence selected from the group consisting of: (a) a polynucleotidefragment of SEQ ID NO:X or a polynucleotide fragment of the cDNAsequence included in ATCC Deposit No:Z, which is hybridizable to SEQ IDNO:X; (b) a polynucleotide encoding a polypeptide fragment of SEQ IDNO:Y or a polypeptide fragment encoded by the cDNA sequence included inATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X; (c) apolynucleotide encoding a polypeptide domain of SEQ ID NO:Y or apolypeptide domain encoded by the cDNA sequence included in ATCC DepositNo:Z, which is hybridizable to SEQ ID NO:X; (d) a polynucleotideencoding a polypeptide epitope of SEQ ID NO:Y or a polypeptide epitopeencoded by the cDNA sequence included in ATCC Deposit No:Z, which ishybridizable to SEQ ID NO:X; (e) a polynucleotide encoding a polypeptideof SEQ ID NO:Y or the cDNA sequence included in ATCC Deposit No:Z, whichis hybridizable to SEQ ID NO:X, having biological activity; (f) apolynucleotide which is a variant of SEQ ID NO:X; (g) a polynucleotidewhich is an allelic variant of SEQ ID NO:X; (h) a polynucleotide whichencodes a species homologue of the SEQ ID NO:Y; (i) a polynucleotidecapable of hybridizing under stringent conditions to any one of thepolynucleotides specified in (a)-(h), wherein said polynucleotide doesnot hybridize under stringent conditions to a nucleic acid moleculehaving a nucleotide sequence of only A residues or of only T residues.2. The isolated nucleic acid molecule of claim 1, wherein thepolynucleotide fragment comprises a nucleotide sequence encoding asecreted protein.
 3. The isolated nucleic acid molecule of claim 1,wherein the polynucleotide fragment comprises a nucleotide sequenceencoding the sequence identified as SEQ ID NO:Y or the polypeptideencoded by the cDNA sequence included in ATCC Deposit No:Z, which ishybridizable to SEQ ID NO:X.
 4. The isolated nucleic acid molecule ofclaim 1, wherein the polynucleotide fragment comprises the entirenucleotide sequence of SEQ ID NO:X or the cDNA sequence included in ATCCDeposit No:Z, which is hybridizable to SEQ ID NO:X.
 5. The isolatednucleic acid molecule of claim 2, wherein the nucleotide sequencecomprises sequential nucleotide deletions from either the C-terminus orthe N-terminus.
 6. The isolated nucleic acid molecule of claim 3,wherein the nucleotide sequence comprises sequential nucleotidedeletions from either the C-terminus or the N-terminus.
 7. A recombinantvector comprising the isolated nucleic acid molecule of claim
 1. 8. Amethod of making a recombinant host cell comprising the isolated nucleicacid molecule of claim
 1. 9. A recombinant host cell produced by themethod of claim
 8. 10. The recombinant host cell of claim 9 comprisingvector sequences.
 11. An isolated polypeptide comprising an amino acidsequence at least 95% identical to a sequence selected from the groupconsisting of: (a) a polypeptide fragment of SEQ ID NO:Y or the encodedsequence included in ATCC Deposit No:Z; (b) a polypeptide fragment ofSEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z,having biological activity; (c) a polypeptide domain of SEQ ID NO:Y orthe encoded sequence included in ATCC Deposit No:Z; (d) a polypeptideepitope of SEQ ID NO:Y or the encoded sequence included in ATCC DepositNo:Z; (e) a secreted form of SEQ ID NO:Y or the encoded sequenceincluded in ATCC Deposit No:Z; (f) a full length protein of SEQ ID NO:Yor the encoded sequence included in ATCC Deposit No:Z; (g) a variant ofSEQ ID NO:Y; (h) an allelic variant of SEQ ID NO:Y; or (i) a specieshomologue of the SEQ ID NO:Y.
 12. The isolated polypeptide of claim 11,wherein the secreted form or the full length protein comprisessequential amino acid deletions from either the C-terminus or theN-terminus.
 13. An isolated antibody that binds specifically to theisolated polypeptide of claim
 11. 14. A recombinant host cell thatexpresses the isolated polypeptide of claim
 11. 15. A method of makingan isolated polypeptide comprising: (a) culturing the recombinant hostcell of claim 14 under conditions such that said polypeptide isexpressed; and (b) recovering said polypeptide.
 16. The polypeptideproduced by claim
 15. 17. A method for preventing, treating, orameliorating a medical condition, comprising administering to amammalian subject a therapeutically effective amount of the polypeptideof claim
 1. 18. A method for preventing, treating, or ameliorating amedical condition, comprising administering to a mammalian subject atherapeutically effective amount of the polypeptide of claim
 11. 19. Amethod of diagnosing a pathological condition or a susceptibility to apathological condition in a subject comprising: (a) determining thepresence or absence of a mutation in the polynucleotide of claim 1; and(b) diagnosing a pathological condition or a susceptibility to apathological condition based on the presence or absence of saidmutation.
 20. A method of diagnosing a pathological condition or asusceptibility to a pathological condition in a subject comprising: (a)determining the presence or amount of expression of the polypeptide ofclaim 11 in a biological sample; and (b) diagnosing a pathologicalcondition or a susceptibility to a pathological condition based on thepresence or amount of expression of the polypeptide.
 21. A method foridentifying a binding partner to the polypeptide of claim 11 comprising:(a) contacting the polypeptide of claim 11 with a binding partner; and(b) determining whether the binding partner effects an activity of thepolypeptide.
 22. The gene corresponding to the cDNA sequence of SEQ IDNO:Y.
 23. A method of identifying an activity in a biological assay,wherein the method comprises: (a) expressing SEQ ID NO:X in a cell; (b)isolating the supernatant; (c) detecting an activity in a biologicalassay; and (d) identifying the protein in the supernatant having theactivity.
 24. The product produced by the method of claim 21.